| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1997;64:715-720
© 1997 The Society of Thoracic Surgeons
Division of Cardiac Anesthesia, Department of Anesthesiology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Division of Neurology, Department of Medicine, Department of Neurobiology, Department of Psychiatry, and Department of Surgery, Duke University Medical Center, Durham, North Carolina
Accepted for publication June 30, 1997.
 |
Abstract |
|---|
 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
4 allele are genetically predisposed to cognitive dysfunction after cardiac operations.
Methods. The apolipoprotein E-4 allele was evaluated as a predictor variable for postoperative cognitive dysfunction in 65 patients undergoing cardiac bypass grafting at Duke University Medical Center. The primary outcome measure was performance on a cognitive battery administered preoperatively and at 6 weeks postoperatively.
Results. In a multivariable logistic regression analysis including apolipoprotein E-4, preoperative score, age, and years of education, a significant association was found between apolipoprotein E-4 and change in cognitive test score in measures of short-term memory at 6 weeks postoperatively. Patients with lower educational levels were more likely to show a decline in cognitive function associated with the apolipoprotein E-4 allele.
Conclusions. This study suggests that apolipoprotein E genotype is related to cognitive dysfunction after cardiopulmonary bypass. Cardiac surgical patients may be susceptible to deterioration after physiologic stress as a result of impaired genetically determined neuronal mechanisms of maintenance and repair.
|
Introduction |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
We hypothesized that variant forms of the apolipoprotein E (APOE) gene that encodes the APOE protein responsible for repair of neuronal injury would make patients more susceptible to cognitive loss in the postoperative period [5, 6]. This could explain the well-documented susceptibility of surgical patients to impaired cognitive performance in tests of orientation to time and place, and recall of recently acquired verbal information [1, 3]. This hypothesis is supported by recent animal and human studies identifying an important role of APOE in the determination of neurologic injury associated with acute ischemic insults and stress, including markedly greater mortality and reduction in functional recovery in patients with intracerebral hemorrhage and closed head injury who possess the APOE -4 allele [7–10].
|
Material and Methods |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
). Patients with a history of cerebrovascular disease, psychiatric illness, renal disease, or active liver disease and those with less than a seventh-grade education were excluded from our investigation. Apolipoprotein E genotyping was accomplished post hoc on a total of 65 patients.
|
Intraoperative Management
Cardiac operation with cardiopulmonary bypass was managed according to a standard anesthetic regimen. Patients were orally premedicated with diazepam (5 to 15 mg) and methadone (10 to 15 mg) 90 to 120 minutes before induction. Routine monitoring included a radial arterial line, pulmonary artery catheter, five-lead electrocardiogram with continuous ST-segment analysis, pulse oximeter, and end-tidal carbon dioxide monitor. Surgical anesthesia was induced and maintained with midazolam, fentanyl, and vecuronium or pancuronium. Hypothermic cardiopulmonary bypass was maintained at 25° to 32°C using a Cobe CML membrane oxygenator (Cobe Laboratories, Lakewood, CO), Sarns 7000 MDX pump (Sarns Inc, Ann Arbor, MI), and Pall SP 3840 (Pall Biomedical Products Co, Glencove, NY) 40-µm arterial line filters.
Neuropsychological Testing
All patients underwent a battery of neuropsychologic tests. Testing was conducted preoperatively and 6 weeks postoperatively. In most cases, the same examiner administered all examinations. The test battery consisted of seven measures: Trail-Making Test part B (perceptual motor speed); the Digits Forward (short-term auditory memory), Digits Backward (short-term auditory memory), and Digit Symbols (psychomotor speed, visual memory) subtests from the Wechsler Adult Intelligence Scale—Revised; the immediate and delayed components of the Randt Short Story memory test (short-term semantic memory); and Benton Visual Retention (short-term figural memory). These instruments were selected on the basis of (1) appropriateness for assessing certain cognitive functions presumed to be affected by operation, (2) availability of multiple forms for repeated testing, (3) brevity and ease of administration, and (4) use in prior studies of similar subjects permitting ready comparison to data reported previously. Raw scores for each test were used in calculating change in individual measures over time.
Statistical Methods
The cognitive outcomes in this study consisted of pairs of neuropsychological test scores (preoperative paired with 6-week tests). The difference between preoperative and postoperative scores was computed for each patient on each neuropsychological measure. Cognitive decline, a measure of the incidence of significant impairment, was defined as 20% decrement in 20% or more of completed tests [11]. Cognitive impairment index, a continuous measure of the degree or severity of impairment, was defined as the average percent decline from baseline over all tests scored for an individual [11]. Any improvement is counted as zero decline in this average. Patients unable to complete every follow-up test were included in analyses for the tests they did complete.
Genotype was analyzed as a two-level category based on the presence or absence of the 4 allele. Multivariable logistic regression analysis was employed to examine the effect of APOE-4 independent of predictors previously identified as significant on postoperative cognitive decline. Factors previously found to be unimportant in predicting cognitive outcome were not included in the model in consideration of statistical constraints [11]. Covariates in the analysis included baseline performance, age, and years of education. Score on the preoperative Randt Delayed Verbatim test was used to represent baseline performance. To ascertain whether the effect of genotype on cognitive decline varied, depending on either age or years of education, the interactions between genotype and age and genotype and years of education were also tested for significance. Backward variable selection was used to serially remove other nonsignificant factors, until only significant (p < 0.05) factors remained in the model.
Baseline demographic and clinical variables for genotype groups were described for categoric data by summarizing frequencies and percentages and for continuous data as means and standard deviations and as medians and 25th and 75th percentiles. To compare genotype groups, Fisher's exact test was used with categoric factors and a nonparametric Wilcoxon rank-sum test was used to evaluate continuous variables.
|
Results |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
4 positive and negative patients are listed in Table 2. There was no statistically significant difference in any of these descriptive variables or in mean baseline psychometric scores among apolipoprotein E-4 positive and negative patients. Intraoperative variables related to cardiopulmonary bypass were also similar across the patient population (see Table 2).
|
4 allele are presented in Figure 1. Twenty-six percent of the study population carried one copy of the apolipoprotein E-4 allele, giving an allelic frequency of 0.13. Because of the small number of 2/3 and 2/4 heterozygotes and the absence of 2/2 and 4/4 homozygotes, 2/3 and 3/3 individuals were grouped as 4 allele absent, and 2/4 and 3/4 individuals were grouped as 4 allele present for later analyses.
|
4 allele and risk of cognitive impairment at 6 weeks. In the presence of APOE-4 allele, age was not found significant and was dropped from the final model. The effect of the 4 allele depended on educational level. For individuals without the 4 allele, there was an increasing risk of impairment with decreasing educational level. In patients with the 4 allele, however, this effect was much more marked, such that risk was significantly greater at lower educational levels in those patients with the 4 allele.
The assessment of the severity of cognitive decline at 6 weeks, the cognitive impairment index, yielded similar relationships. Multivariable linear regression on 6-week cognitive impairment index indicated a significant association between the presence of the apolipoprotein E-4 allele and the severity of cognitive impairment. Educational level again modulated the extent of this effect. Details of the logistic and linear regression analyses are shown in Table 3.
|
|
Comment |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
4, suggesting that events during operation caused the decline in cognitive function in genetically susceptible patients. The memory and cognition changes described after cardiac operations are similar in some respects to those seen in early stage of chronic dementias such as Alzheimer's disease [12–14]. In addition, patients with a higher level of education appear to be less susceptible to both Alzheimer's disease and postbypass neurodysfunction [4, 15], either due to enhanced coping skills or undefined physiologic or biochemical mechanisms.
Limitations
A number of limitations apply to this preliminary study. Because the study was observational, significant effects can be interpreted as associations, but no assumption of causality can be proven and inferences are limited to a similar population of cardiac surgery patients. The relatively small sample size in this initial study limited the number of predictors that could be included in the model and restricts the power of the conclusions. Larger studies are required that will have statistical power to support stronger inferences.
Follow-up was incomplete for some patients, which can introduce selection bias. Separate analyses for each cognitive outcome were performed, so that as much information as possible could be used. The absence of complete follow-up data beyond 6 weeks limits our ability to draw conclusions regarding long-term impact.
Apolipoprotein E in Other Clinical Settings
The observed frequency of 0.13 for apolipoprotein E-4 is identical to the allelic frequency seen in several normal control populations studied at Duke University [5] and comparable with the allele frequency of other large unrelated populations [16, 17]. The lack of 2/2 and 4/4 homozygotes and relative infrequency of the 2/3 and 2/4 genotypes is not unexpected given their low frequencies in the population.
The association between APOE and reparative mechanisms in chronic degenerative diseases has led to intense investigation of APOE's role in acute neurologic injury. Alberts and associates [10] reported death rate and functional recovery in a series of patients with intracerebral hemorrhage, where the acute death rate is usually 50%. Patients with the 3/4 genotype had a 70% death rate and those who lived did not functionally recover. The 3/3 patients had a 30% death rate, and the functional recovery was excellent. The presence of the APOE 4 allele was also associated with worsened recovery and outcome in patients experiencing head trauma [8, 18]. Experimental data in APOE deficient wild-type mice showed that the lack of the normal APOE locus resulted in increased infarct size in a middle cerebral artery occlusion model, further supporting the role of APOE in determining cell recovery from central nervous system ischemia or stress [7].
Our postoperative cognitive outcome results are remarkably consistent with these experimental data. Neuropsychological testing showed no differences in patients with and without the -4 allele at baseline but demonstrated a greater susceptibility to decline with the central nervous system insult imparted by cardiopulmonary bypass.
Although some investigations have demonstrated an association of apolipoprotein E-4 allele with elevated levels of plasma cholesterol, low-density lipoprotein-cholesterol, and triglyceride [19, 20], and accelerated coronary artery disease [21] compared with age-matched controls, this has not been a consistent finding by all investigators or in all populations [22, 23]. Although we cannot rule out increased atherosclerosis as the mechanism producing increased decline in cognitive function, it appears that the risk for cognitive change after cardiopulmonary bypass associated with the apolipoprotein E-4 allele is far more complex than hyperlipidemia [20, 24].
Significance
One can speculate that the mechanisms of neuronal maintenance or repair capacity may be impaired in individuals with the 4 allele. An understanding of how damage is related to impaired homeostatic processes should facilitate further investigation into the etiology of postoperative dysfunction and will be critical to the design of effective strategies for prevention of postoperative deficits. The very interesting association observed between apolipoprotein E-4 and cognitive decline after cardiac operations holds promise for an entire new approach to the prediction and, more important, prevention of neurocognitive dysfunction after cardiac operations.
|
Appendix 1. Neurologic Outcome Research Group of the Duke Heart Center |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
Anesthesiology: Bea Baldwin, CRNA; Narda D. Croughwell, CRNA; Elizabeth deLong, PhD; Jerry L. Kirchner, BS; Hilary Grocott, MD; Bruce J. Leone, MD; Mark F. Newman, MD; Joseph G. Reves, MD; Barbara E. Tardiff, MD; William D. White, MPH
Behavioral Science: Michael Babyak, PhD; James A. Blumenthal, PhD; Eileen Burker, PhD; Heather Fraser, BA; Elizabeth P. Mahanna, BA; Elizabeth A. Thyrum, PhD; Carolina P. Clancey, BA
Surgery: R. Duane Davis, Jr, MD; Donald D. Glower, MD; Robert H. Jones, MD; Kevin P. Landolfo, MD; Peter K. Smith, MD
Medicine: Nancy Clapp-Channing, MS; Barrie J. Hurwitz, MD; Daniel B. Mark, MD; William Spillane, MD; Warren J. Strittmatter, MD; Ann M. Saunders, PhD; Allen D. Roses, MD
|
Acknowledgments |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
We appreciate the enthusiastic support and cooperation of our surgical colleagues: Drs Robert W. Anderson, R. Duane Davis, Jr, Francis G. Duhaylongsod, Donald D. Glower, Jr, James Jaggers, Robert H. Jones, Kevin P. Landolfo, James E. Lowe, Peter K. Smith, and Walter G. Wolfe. We also acknowledge the support of our perfusionist colleagues: Ian Shearer, C. B. Clark, Edward Darling, Joyce Hancock, Curtis King, D. Scott Lawson, Tim Moretz, Katherine Nanry, Carmen Offer, Calvin Rogers, and Greg Smigla. We thank Ed Lowry for assistance in data collection and Kathleen A. Welsh, PhD, for valuable discussion in the preparation of the manuscript.
|
Footnotes |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
* The members of the Neurologic Outcome Research Group of the Duke Heart Center are listed in Appendix 1. 
|
References |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAppendix 1. Neurologic Outcome...AcknowledgmentsReferences |
|---|
4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993;43:1467–72.This article has been cited by other articles:
|
|
 |
|
  L. A. Evered, B. S. Silbert, D. A. Scott, P. Maruff, K. M. Laughton, I. Volitakis, T. Cowie, R. A. Cherny, C. L. Masters, and Q.-X. Li Plasma Amyloid beta(42) and Amyloid beta(40) Levels Are Associated With Early Cognitive Dysfunction After Cardiac Surgery. Ann. Thorac. Surg., November 1, 2009; 88(5): 1426 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, R. A. Zimmerman, G. P. Jarvik, A. S. Nord, R. R. Clancy, G. Wernovsky, L. M. Montenegro, D. M. Hartman, S. C. Nicolson, T. L. Spray, et al. Perioperative stroke in infants undergoing open heart operations for congenital heart disease. Ann. Thorac. Surg., September 1, 2009; 88(3): 823 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fuller, A. S. Nord, M. Gerdes, G. Wernovsky, G. P. Jarvik, J. Bernbaum, E. Zackai, and J. W. Gaynor Predictors of impaired neurodevelopmental outcomes at one year of age after infant cardiac surgery Eur. J. Cardiothorac. Surg., July 1, 2009; 36(1): 40 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Gaynor, A. S. Nord, G. Wernovsky, J. Bernbaum, C. B. Solot, N. Burnham, E. Zackai, P. J. Heagerty, R. R. Clancy, S. C. Nicolson, et al. Apolipoprotein E Genotype Modifies the Risk of Behavior Problems After Infant Cardiac Surgery Pediatrics, July 1, 2009; 124(1): 241 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Silbert, L. A. Evered, D. A. Scott, and T. F. Cowie The Apolipoprotein E {epsilon}4 Allele is not Associated With Cognitive Dysfunction in Cardiac Surgery Ann. Thorac. Surg., September 1, 2008; 86(3): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Hogue, R. Fucetola, T. Hershey, K. Freedland, V. G. Davila-Roman, A. M. Goate, and R. E. Thompson Risk Factors for Neurocognitive Dysfunction After Cardiac Surgery in Postmenopausal Women Ann. Thorac. Surg., August 1, 2008; 86(2): 511 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Zeltser, G. P. Jarvik, J. Bernbaum, G. Wernovsky, A. S. Nord, M. Gerdes, E. Zackai, R. Clancy, S. C. Nicolson, T. L. Spray, et al. Genetic factors are important determinants of neurodevelopmental outcome after repair of tetralogy of Fallot J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Savino and A. T. Cheung Cardiac Anesthesia Card. Surg. Adult, January 1, 2008; 3(2008): 281 - 314. [Full Text]
|
|
|
|
|
|
J. W. Hammon Extracorporeal Circulation: Organ Damage Card. Surg. Adult, January 1, 2008; 3(2008): 389 - 414. [Full Text]
|
|
|
|
|
|
O. A. Selnes, M. A. Grega, M. M. Bailey, L. Pham, S. Zeger, W. A. Baumgartner, and G. M. McKhann Neurocognitive Outcomes 3 Years After Coronary Artery Bypass Graft Surgery: A Controlled Study Ann. Thorac. Surg., December 1, 2007; 84(6): 1885 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. I. Tagarakis, F. Tsolaki-Tagaraki, M. Tsolaki, A. Diegeler, N. B. Tsilimingas, and A. Papassotiropoulos The Role of Apolipoprotein E in Cognitive Decline and Delirium after Bypass Heart Operations American Journal of Alzheimer's Disease and Other Dementias, July 1, 2007; 22(3): 223 - 228. [Abstract] [PDF]
|
|
|
|
|
|
J. W. Gaynor, G. Wernovsky, G. P. Jarvik, J. Bernbaum, M. Gerdes, E. Zackai, A. S. Nord, R. R. Clancy, S. C. Nicolson, and T. L. Spray Patient characteristics are important determinants of neurodevelopmental outcome at one year of age after neonatal and infant cardiac surgery J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1344 - 1353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Dorotta, P. Kimball-Jones, and R. Applegate II Deep hypothermia and circulatory arrest in adults. Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2007; 11(1): 66 - 76. [Abstract] [PDF]
|
|
|
|
|
|
H. P. Grocott Genetic influences on cerebral outcome after cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 291 - 296. [Abstract] [PDF]
|
|
|
|
 |
|
 E. R. Marcantonio, J. L. Rudolph, D. Culley, G. Crosby, D. Alsop, and S. K. Inouye Review Article: Serum Biomarkers for Delirium J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2006; 61(12): 1281 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Szalma, A. Kiss, L. Kardos, G. Horvath, E. Nyitrai, Z. Tordai, and L. Csiba Piracetam prevents cognitive decline in coronary artery bypass: a randomized trial versus placebo. Ann. Thorac. Surg., October 1, 2006; 82(4): 1430 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Mahley, K. H. Weisgraber, and Y. Huang Inaugural Article: Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer's disease PNAS, April 11, 2006; 103(15): 5644 - 5651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Smith, D I Graham, L S Murray, J Stewart, and J A R Nicoll Association of APOE e4 and cerebrovascular pathology in traumatic brain injury. J. Neurol. Neurosurg. Psychiatry, March 1, 2006; 77(3): 363 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Heyer, D. A. Wilson, D. H. Sahlein, J. Mocco, S. C. Williams, R. Sciacca, A. Rampersad, R. J. Komotar, J. Zurica, A. Benvenisty, et al. APOE-{varepsilon}4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy Neurology, December 13, 2005; 65(11): 1759 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Podgoreanu and D. A. Schwinn New Paradigms in Cardiovascular Medicine: Emerging Technologies and Practices: Perioperative Genomics J. Am. Coll. Cardiol., December 6, 2005; 46(11): 1965 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Grocott, W. D. White, R. W. Morris, M. V. Podgoreanu, J. P. Mathew, D. M. Nielsen, D. A. Schwinn, M. F. Newman, and for the Perioperative Genetics and Safety Outcomes Genetic Polymorphisms and the Risk of Stroke After Cardiac Surgery Stroke, September 1, 2005; 36(9): 1854 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Grocott, H. M. Homi, and F. Puskas Cognitive Dysfunction After Cardiac Surgery: Revisiting Etiology Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2005; 9(2): 123 - 129. [Abstract] [PDF]
|
|
|
|
|
|
W. A. Kofke, A. Cheung, and P. Konitzer Apolipoprotein E Genotype and S100{beta} After Cardiac Surgery: Is Inflammation the Link? Anesth. Analg., June 1, 2005; 100(6): 1870 - 1870. [Full Text] [PDF]
|
|
|
|
|
|
H. P. Grocott and G. B. Mackensen Apolipoprotein E Genotype and S100{beta} After Cardiac Surgery: Is Inflammation the Link? Anesth. Analg., June 1, 2005; 100(6): 1869 - 1870. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pomara, L. Willoughby, K. Wesnes, D. J. Greenblatt, and J. J. Sidtis Apolipoprotein E {varepsilon}4 Allele and Lorazepam Effects on Memory in High-Functioning Older Adults Arch Gen Psychiatry, February 1, 2005; 62(2): 209 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wahrborg, J. E. Booth, T. Clayton, F. Nugara, J. Pepper, W. S. Weintraub, U. Sigwart, R. H. Stables, and for the SoS Neuropsychology Substudy Investigators Neuropsychological Outcome After Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Results From the Stent or Surgery (SoS) Trial Circulation, November 30, 2004; 110(22): 3411 - 3417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bar-Yosef, M. Anders, G. B. Mackensen, L. K. Ti, J. P. Mathew, B. Phillips-Bute, R. H. Messier, H. P. Grocott, and the Neurological Outcome Research Group and CARE I Aortic Atheroma Burden and Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery Ann. Thorac. Surg., November 1, 2004; 78(5): 1556 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Kofke, P. Konitzer, Q. C. Meng, J. Guo, and A. Cheung The Effect of Apolipoprotein E Genotype on Neuron Specific Enolase and S-100{beta} Levels After Cardiac Surgery Anesth. Analg., November 1, 2004; 99(5): 1323 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Homi, H. Yang, R. D. Pearlstein, and H. P. Grocott Hemodilution During Cardiopulmonary Bypass Increases Cerebral Infarct Volume After Middle Cerebral Artery Occlusion in Rats Anesth. Analg., October 1, 2004; 99(4): 974 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Hays, B. M. Burchett, G. G. Fillenbaum, and D. G. Blazer Is the APOE {epsilon}4 Allele a Risk to Person-Environment Fit? Journal of Applied Gerontology, September 1, 2004; 23(3): 247 - 265. [Abstract] [PDF]
|
|
|
|
|
|
R. G. Cutler, N. J. Haughey, A. Tammara, J. C. McArthur, A. Nath, R. Reid, D. L. Vargas, C. A. Pardo, and M. P. Mattson Dysregulation of sphingolipid and sterol metabolism by ApoE4 in HIV dementia Neurology, August 24, 2004; 63(4): 626 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Podgoreanu and D. A. Schwinn Genomics and the circulation Br. J. Anaesth., July 1, 2004; 93(1): 140 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Raber Androgens, ApoE, and Alzheimer's Disease Sci. Aging Knowl. Environ., March 17, 2004; 2004(11): re2 - re2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Hammon Risk Factors for Cardiac Surgery: The High-Risk Patient Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2004; 8(1): 15 - 17. [Abstract] [PDF]
|
|
|
|
|
|
K. K. Galli, R. A. Zimmerman, G. P. Jarvik, G. Wernovsky, M. K. Kuypers, R. R. Clancy, L. M. Montenegro, W. T. Mahle, M. F. Newman, A. M. Saunders, et al. Periventricular leukomalacia is common after neonatal cardiac surgery J. Thorac. Cardiovasc. Surg., March 1, 2004; 127(3): 692 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ho, D. B. Arciniegas, J. Grigsby, M. McCarthy Jr, G. O. McDonald, T. E. Moritz, A. L. Shroyer, G. K. Sethi, W. G. Henderson, M. J. London, et al. Predictors of cognitive decline following coronary artery bypass graft surgery Ann. Thorac. Surg., February 1, 2004; 77(2): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Gaynor, M. Gerdes, E. H. Zackai, J. Bernbaum, G. Wernovsky, R. R. Clancy, M. F. Newman, A. M. Saunders, P. J. Heagerty, J. A. D'Agostino, et al. Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1736 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kay, A. Petzold, M. Kerr, G. Keir, E. Thompson, and J. Nicoll Decreased Cerebrospinal Fluid Apolipoprotein E After Subarachnoid Hemorrhage: Correlation With Injury Severity and Clinical Outcome Stroke, March 1, 2003; 34(3): 637 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Haddock, W. S. C. Poston, and J. E. Taylor Neurocognitive Sequelae Following Coronary Artery Bypass Graft: A Research Agenda for Behavioral Scientists Behav Modif, January 1, 2003; 27(1): 68 - 82. [Abstract] [PDF]
|
|
|
|
|
|
L. K. Ti, G. B. Mackensen, H. P. Grocott, D. T. Laskowitz, B. G. Phillips-Bute, C. A. Milano, A. K. Hilton, M. F. Newman, and J. P. Mathew Apolipoprotein E4 increases aortic atheroma burden in cardiac surgical patients J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 211 - 213. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Savino, T. F. Floyd, and A. T. Cheung Cardiac Anesthesia Card. Surg. Adult, January 1, 2003; 2(2003): 249 - 281. [Full Text]
|
|
|
|
|
|
J. W. Hammon Jr. and L. H. Edmunds Jr. Extracorporeal Circulation: Organ Damage Card. Surg. Adult, January 1, 2003; 2(2003): 361 - 388. [Full Text]
|
|
|
|
 |
|
 J. A. Morrow, D. M. Hatters, B. Lu, P. Hochtl, K. A. Oberg, B. Rupp, and K. H. Weisgraber Apolipoprotein E4 Forms a Molten Globule. A POTENTIAL BASIS FOR ITS ASSOCIATION WITH DISEASE J. Biol. Chem., December 20, 2002; 277(52): 50380 - 50385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ascione, B. C. Reeves, M. H. Chamberlain, A. K. Ghosh, K. H.H. Lim, and G. D. Angelini Predictors of stroke in the modern era of coronary artery bypass grafting: a case control study Ann. Thorac. Surg., August 1, 2002; 74(2): 474 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ascione, S. Al-Ruzzeh, K. Amer, and G. D Angelini Subsystem organ function during coronary surgery Perfusion, July 1, 2002; 17(4): 295 - 303. [Abstract] [PDF]
|
|
|
|
|
|
M. Swaminathan, B. J. McCreath, B. G. Phillips-Bute, M. F. Newman, J. P. Mathew, P. K. Smith, J. A. Blumenthal, and M. Stafford-Smith Serum Creatinine Patterns in Coronary Bypass Surgery Patients With and Without Postoperative Cognitive Dysfunction Anesth. Analg., July 1, 2002; 95(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sato, D. T. Laskowitz, E. R. Bennett, M. F. Newman, D. S. Warner, and H. P. Grocott Differential Cerebral Gene Expression During Cardiopulmonary Bypass in the Rat: Evidence for Apoptosis? Anesth. Analg., June 1, 2002; 94(6): 1389 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M J A Robson, R P Alston, P J D Andrews, P R Wenham, M J Souter, and I J Deary Apolipoprotein E and neurocognitive outcome from coronary artery surgery J. Neurol. Neurosurg. Psychiatry, May 1, 2002; 72(5): 675 - 676. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Murkin Attenuation of neurologic injury during cardiac surgery Ann. Thorac. Surg., November 1, 2001; 72(5): S1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Grocott, M. F. Newman, H. El-Moalem, D. Bainbridge, A. Butler, and D. T. Laskowitz Apolipoprotein E genotype differentially influences the proinflammatory and anti-inflammatory response to cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., September 1, 2001; 122(3): 622 - 623. [Full Text] [PDF]
|
|
|
|
|
|
L. K. Ti, J. P. Mathew, G. B. Mackensen, H. P. Grocott, W. D. White, J. G. Reves, and M. F. Newman Effect of Apolipoprotein E Genotype on Cerebral Autoregulation During Cardiopulmonary Bypass Stroke, July 1, 2001; 32(7): 1514 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Niskakangas, J. Ohman, M. Niemela, E. Ilveskoski, T. A. Kunnas, and P. J. Karhunen Association of Apolipoprotein E Polymorphism With Outcome After Aneurysmal Subarachnoid Hemorrhage : A Preliminary Study Stroke, May 1, 2001; 32(5): 1181 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Selnes, R. M. Royall, M. A. Grega, L. M. Borowicz Jr, S. Quaskey, and G. M. McKhann Cognitive Changes 5 Years After Coronary Artery Bypass Grafting: Is There Evidence of Late Decline? Arch Neurol, April 1, 2001; 58(4): 598 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Steed, R. Kong, J. Stygall, J. Acharya, M. Bolla, M. J.G. Harrison, S. E. Humphries, and S. P. Newman The role of apolipoprotein E in cognitive decline after cardiac operation Ann. Thorac. Surg., March 1, 2001; 71(3): 823 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chapman, S. Vinokurov, A. Achiron, D. M. Karussis, K. Mitosek-Szewczyk, M. Birnbaum, D. M. Michaelson, and A. D. Korczyn APOE genotype is a major predictor of long-term progression of disability in MS Neurology, February 13, 2001; 56(3): 312 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Bedlack, W. J. Strittmatter, and J. C. Morgenlander Apolipoprotein E and Neuromuscular Disease: A Critical Review of the Literature Arch Neurol, November 1, 2000; 57(11): 1561 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Tesseur, J. Van Dorpe, K. Bruynseels, F. Bronfman, R. Sciot, A. Van Lommel, and F. Van Leuven Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord Am. J. Pathol., November 1, 2000; 157(5): 1495 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. van Dijk, A. M. A. Keizer, J. C. Diephuis, C. Durand, L. J. Vos, and R. Hijman Neurocognitive dysfunction after coronary artery bypass surgery: A systematic review J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 632 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Laskowitz, D. M. Lee, D. Schmechel, and H. F. Staats Altered immune responses in apolipoprotein E-deficient mice J. Lipid Res., April 1, 2000; 41(4): 613 - 620. [Abstract] [Full Text]
|
|
|
|
|
|
I. Tesseur, J. Van Dorpe, K. Spittaels, C. Van den Haute, D. Moechars, and F. Van Leuven Expression of Human Apolipoprotein E4 in Neurons Causes Hyperphosphorylation of Protein Tau in the Brains of Transgenic Mice Am. J. Pathol., March 1, 2000; 156(3): 951 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Lloyd, R. Ascione, M. J. Underwood, F. Gardner, A. Black, and G. D. Angelini SERUM S-100 PROTEIN RELEASE AND NEUROPSYCHOLOGIC OUTCOME DURING CORONARY REVASCULARIZATION ON THE BEATING HEART: A PROSPECTIVE RANDOMIZED STUDY J. Thorac. Cardiovasc. Surg., January 1, 2000; 119(1): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chapman, C. Sylantiev, P. Nisipeanu, and A. D. Korczyn Preliminary Observations on APOE{epsilon}4 Allele and Progression of Disability in Multiple Sclerosis Arch Neurol, December 1, 1999; 56(12): 1484 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Selnes, M. A. Goldsborough, L. M. Borowicz Jr, C. Enger, S. A. Quaskey, and G. M. McKhann Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem Ann. Thorac. Surg., June 1, 1999; 67(6): 1669 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sheng, D. T. Laskowitz, G. B. Mackensen, M. Kudo, R. D. Pearlstein, D. S. Warner, and C. Iadecola Apolipoprotein E Deficiency Worsens Outcome From Global Cerebral Ischemia in the Mouse • Editorial Comment Stroke, May 1, 1999; 30(5): 1118 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Newman, D. T. Laskowitz, A. M. Saunders, A. M. Grigore, and H. P. Grocott Genetic Predictors of Perioperative Neurologic and Neuropsychological Injury and Recovery Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 1999; 3(1): 34 - 46. [Abstract] [PDF]
|
|
|
|
|
|
P.-T. Xu, J. R. Gilbert, H.-L. Qiu, J. Ervin, T. R. Rothrock-Christian, C. Hulette, and D. E. Schmechel Specific Regional Transcription of Apolipoprotein E in Human Brain Neurons Am. J. Pathol., February 1, 1999; 154(2): 601 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sun, S. Wu, G. Bu, M. K. Onifade, S. N. Patel, M. J. LaDu, A. M. Fagan, and D. M. Holtzman Glial Fibrillary Acidic Protein-Apolipoprotein E (apoE) Transgenic Mice: Astrocyte-Specific Expression and Differing Biological Effects of Astrocyte-Secreted apoE3 and apoE4 Lipoproteins J. Neurosci., May 1, 1998; 18(9): 3261 - 3272. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
