Skills vs. seniority: the logic of layoffs.
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Bed Occupancy↗
Biomedical subjects
E Dunn
Publications and source records attributed to E Dunn.
Early versus delayed repair of facial fractures in the multiply injured patient.
The management of facial fractures in the polytrauma patient requires the coordination of multiple surgical disciplines to optimize the functional and cosmetic outcome while minimizing overall morbidity and mortality. Although the plastic surgery literature historically advocates the early repair of facial fractures, the risk of general anesthesia in patients with associated injuries sometimes makes early repair unsafe. We compared early operative repair versus delayed operative repair of facial fractures in multitrauma patients. We specifically examined wound infection, overall complication rate, total length of hospital stay, days in the Intensive Care Unit (ICU), and days on the ventilator in the two groups. A 5-year (1991-1996) retrospective study of multitrauma patients with associated facial fractures was undertaken at an urban community hospital. We had a total of 82 patients, who were divided into three groups. Thirty-three patients did not have operative repair of the facial fractures during the initial admission and were followed by the plastic surgery service on an outpatient basis. These patients will not be discussed further. Seven patients underwent early operative repair, which was defined as repair within 48 hours of admission (group I). Forty-two patients had delayed operative repair, defined as repair more than 48 hours after admission (group II). The reasons for delayed repair included: excessive soft tissue swelling (16), intracranial injuries (12), unstable medical condition (8), and coordination of procedures with other services (6). Of the 49 patients who underwent operative repair, 43 were involved in motor vehicle accidents, 3 were injured by a fall from a height, 2 were involved in auto-pedestrian accidents, and 1 was a victim of assault. Forty-eight of the 49 patients were initially admitted to the ICU. Cumulative associated injuries were as follows: closed head injury (38), extremity fracture (21), blunt chest injuries (11), intra-abdominal injuries (5), vertebral column injuries (7), and ocular injuries (2). The average Injury Severity Score for Group I was 17.3 and for Group II, 18.1. In group I, there were no deaths, there were no wound infections, and the complication rate was 14.3 per cent. The average total number of days spent on the ventilator was 3.0, the average total number of days spent in the ICU was 5.0, and the average total hospital stay was 16.0 days. In group II, there were no deaths, the wound infection rate was 5 per cent, and the overall complication rate was 21 per cent. The average total number of days spent on the ventilator was 3.3, the average total number of days spent in the ICU was 5.8, and the average total days in the hospital was 14.8. Our results indicate that in a similar cohort of multitrauma patients, delayed repair did not increase length of ICU stay or hospital stay. The wound infection rate was negligible, and the complication rate was similar in the two groups. We conclude that a delay in repair of facial fractures in the critically ill patient has an acceptably low complication rate and may be advantageous in decreasing operative risk and minimizing cost by coordinating multiple procedures with various surgical subspecialties.
Adolescent↗
The translation into Arabic and revalidation of a fatigue questionnaire.
The aim of this study was to translate a fatigue questionnaire, which had been developed in England for use in epidemiological studies and in community settings, into Arabic. It was intended that the translated questionnaire could be used in any setting where Arabic is the first language of the patient. The process of translating the questionnaire and the revalidation method are described. The Arabic translation was shown to be both reliable and valid in the United Arab Emirates setting.
Adult↗
Visual outcomes of cataract surgery in the United States, Canada, Denmark, and Spain. Report From the International Cataract Surgery Outcomes Study.
OBJECTIVE: To compare visual outcomes obtained following cataract surgery in 4 sites in North America and Europe where considerable differences in the organization of care and patterns of clinical practice have been previously described. METHODS: Patients scheduled for first eye-cataract surgery and aged 50 years or older were enrolled consecutively in a prospective multicenter study that collected clinical and patient interview data preoperatively and postoperatively. From the United States, 772 patients were enrolled; from the Province of Manitoba (Canada), 159; from Denmark, 291; and from the City of Barcelona (Spain), 200. Preoperative and 4-month postoperative visual acuity was obtained for 92% of the patients (n = 1291). RESULTS: The mean 4-month postoperative visual acuity of eyes operated on varied significantly across the 4 sites (P < .001) and had the following Snellen decimal fraction measurements: 0.49 in Barcelona, 0.65 in Denmark, 0.66 in Manitoba, and 0.74 in the United States. However, while crude visual acuity outcome figures varied significantly, no significant difference was observed across the 4 sites regarding the risk of poorer visual outcome after controlling for differences in age, preoperative visual acuity, and general health status for patients with no ocular comorbidity. Older age, poorer preoperative visual acuity, poorer preoperative general health status, and coexisting ocular comorbidity were predictors of a poorer visual outcome. CONCLUSION: A previously identified variation in treatment modalities across the 4 sites did not seem to affect patients' visual acuity outcomes.
Aged↗
Self and tutor evaluations in problem-based learning tutorials: is there a relationship?
It is now recognized that acquiring specific skills in self-evaluation helps students in a more general appraisal of their overall performance. Self- and peer-evaluation skills are essential prerequisites for the success of every doctor in maintaining professional competence. In the Faculty of Medicine and Health Sciences (FMHS) of the United Arab Emirates, problem-based learning (PBL) is instituted in the first year. Self-evaluation by students and tutor rating of students' performances are an integral part of the PBL tutorials. This has provided the opportunity to conduct a systematic study of the role of self-evaluation by students as distinct from the tutor evaluation of students in the PBL tutorials for five themes. The study sample included all preparatory year (first-year) students who joined the FMHS in 1994 and 1995. A total number of 64 students participated, of whom 17 (26%) were male and 47 (74%) female. Mean self-evaluation scores were high throughout the module and did not follow any trend from theme one to theme five. While self and tutor scores were similar, male student self-evaluation scores were higher than for female students on overall scores. The sharing of assessment reports between students and tutors has been perceived to be a useful tool for the students' development of the skills of analysis, differentiation and critical appraisal.
Adult↗
Facility with the English language and problem-based learning group interaction: findings from an Arabic setting.
The Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates (UAE) University is in a unique position to explore issues related to English language proficiency and medical student performance. All students entering the FMHS have English as a second language. This study focused on the issues of students' proficiency in English as measured by the TOEFL test, student background factors and interaction in problem-based learning (PBL) groups. Using a modification of Bales Interaction Process Analysis, four problem-based learning groups were observed over four thematic units, to measure the degree of student interaction within PBL groups and to compare this to individual TOEFL scores and key background variables. The students' contributions correlated highly with TOEFL test results in the giving of information (range r = 0.67-0.74). The female students adhered to interacting in English during group sessions, whereas the male students were more likely to revert to using Arabic in elaborating unclear phenomena (p < 0.01). The educational level of the student's mother was highly predictive of TOEFL scores for the male students, but not for female students. Multivariate analysis was undertaken to analyse the relative contribution of the TOEFL, parental education and years of studying in English. The best predictor of students' contributions in PBL groups was identified as TOEFL scores. The study demonstrates the importance of facilitating a locally acceptable level of English proficiency prior to admission to the FMHS. However, it also highlights the importance of not focusing only on English proficiency but paying attention to additional factors in facilitating medical students in maximizing benefits from interactions in PBL settings.
Clinical Competence↗
Neuroprotective efficacy and mechanisms of novel pyrrolopyrimidine lipid peroxidation inhibitors in the gerbil forebrain ischemia model.
A brief period of bilateral carotid occlusion (BCO)-induced forebrain ischemia in gerbils triggers neuronal degeneration and the subsequent expression of amyloid precursor protein (APP), b-amyloid protein (b-AP), and apolipoprotein E (APO-E) in the selectively vulnerable CA1 region of the hippocampus. The increase in immunoreactivity is secondary to the postischemic degeneration of the CA1 neurons and is largely astrocyte-derived as evidenced by a simultaneous increase in glial fibrillary acidic protein (GFAP) staining. Oxygen radical-induced lipid peroxidation has been strongly suggested to play a role in postischemic neuronal damage and Alzheimer's disease. Recent literature suggests a possible link between early oxidative stress and APP overexpression. Therefore, the present investigation examined the effect of two novel brain-penetrating pyrrolopyrimidine lipid peroxidation inhibitors (PNU-101033E and PNU-104067F) on CA1 neurodegeneration and the subsequent increase in APP, b-AP, APO-E, and GFAP immunostaining at 4 days after a 5-minute episode of forebrain ischemia. Using an antibody for lipid peroxidation-derived malondialdehyde (MDA)-modified proteins, the authors also examined the effects of PNU-104067F on MDA immunostaining 2 days after ischemia, before completion of the neuronal loss. At 2 days, the authors also evaluated microglial activation using an antibody to surface major histocompatibility complex class II antigen expressed by activated microglia. Gerbils were treated at 30 mg/kg orally 30 minutes before the BCO and 2 hours after ischemia, followed by daily dosing for the next day (microglia and MDA) and the successive 3 days for APP, b-AP, APO-E, and GFAP immunostaining. APP and APO-E staining was significantly suppressed by 50% and 66%, respectively, with either compound. b-AP immunoreactivity was decreased 56% with both compounds, and GFAP expression was significantly decreased 53% (PNU-101033E) and 60.5% (PNU-104067F). There was a concomitant partial sparing of the CA1 hippocampal neurons by both PNU-101033E and PNU-104067F (P < .01) as determined by cresyl violet histochemistry. PNU-104067F significantly inhibited lipid peroxidation-derived MDA immunostaining and microglia activation (P < .05) at 48 hours after ischemia. Brain-penetrable lipid peroxidation inhibitors may provide attenuation of various glial response proteins after ischemic injury, probably secondary to neuronal protection.
Animals↗
Cross-cultural differences in the reporting of global functional capacity: an example in cataract patients.
OBJECTIVES: Patient-based health status measures have an important role to play in the assessment of health care outcomes. Among these measures, global assessments increasingly have been used, although the understanding of the performance of these indicators and the determinants of patients responses is underdeveloped. In this study, the performance of a single-item global indicator of visual function in cataract patients of four international settings was compared. METHODS: Visual acuity and ocular comorbidity was assessed by patients' ophthalmologist using Snellen-type charts in patients referred for a first cataract surgery in the United States, Manitoba (Canada), Denmark, and Barcelona (Spain). Patients also were interviewed by telephone and asked to report overall trouble with vision on a single-item indicator ("great deal," "moderate," "a little," "none") and to complete the Visual Functioning Index (VF-14), a scale of visual function ranging from 0 (worst function) to 100 (best level of function), along with other questions including the degree the patient was bothered by symptoms as measured by the Cataract Symptom Score (CSS). A total of 1,407 patients completed the clinical examination and the preoperative interview. RESULTS: Distribution of overall trouble with vision varied across the sites, with the proportion of patients reporting a great deal of trouble ranging from 21.7% to 37.9%. In all sites, patients reporting more trouble with vision tended to show a poorer age-adjusted and sex-adjusted visual acuity. The proportion of patients reporting great deal of trouble with vision was higher in the groups with worse visual acuity (P < 0.001). In multivariate analysis, after controlling for clinical and sociodemographic factors, the patients from Manitoba (OR = 0.32, 95% CI = 0.20, 0.51) and those from Barcelona (OR = 0.33, 95% CI = 0.20, 0.56) were less likely to report a great deal of trouble with their vision (P < 0.01) than the Danish and US patients. No such differences were found among the US patients from three sites. CONCLUSIONS: There is international variation in the self-reporting of global vision-related functional capacity that is not explained by clinical or sociodemographic factors, which may be because of cultural differences. International comparisons of patient-based health outcomes should not rely only on single-item indicators until there is convincing evidence of their cross-cultural equivalence.
Activities of Daily Living↗
Variation in indications for cataract surgery in the United States, Denmark, Canada, and Spain: results from the International Cataract Surgery Outcomes Study.
BACKGROUND/AIMS: International comparisons of clinical practice may help in assessing the magnitude and possible causes of variation in cross national healthcare utilisation. With this aim, the indications for cataract surgery in the United States, Denmark, the province of Manitoba (Canada), and the city of Barcelona (Spain) were compared. METHODS: In a prospective multicentre study, patients scheduled for first eye cataract surgery and aged 50 years or older were enrolled consecutively. From the United States 766 patients were enrolled; from Denmark 291; from Manitoba 152; and from Barcelona 200. Indication for surgery was measured as preoperative visual status of patients enlisted for cataract surgery. Main variables were preoperative visual acuity in operative eye, the VF-14 score (an index of functional impairment in patients with cataract) and ocular comorbidity. RESULTS: Mean visual acuity were 0.23 (USA), 0.17 (Denmark), 0.15 (Manitoba), and 0.07 (Barcelona) (p < 0.001). When restricting the sample to eyes with normal retina and macula, no significant difference between United States and Denmark was observed (p > 0.05). Mean VF-14 scores were 76 (USA), 76 (Denmark), 71 (Manitoba), and 64 (Barcelona) (p < 0.001). CONCLUSION: Similar indications for cataract surgery were found in the United States and Denmark. Significantly more restricted indications were observed in Manitoba and Barcelona. Possible explanations for the results are discussed, including differences in sociodemographic characteristics, access to care, surgeons' willingness to operate, and patient demand.
Aged↗
Derek E Denny-Brown (1901-1981): his life and influence on American neurology.
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History, 19th Century↗
Domain specificity of the subtests of the Mini-Mental State Examination.
OBJECTIVE: To examine the convergent and, for the first time to our knowledge, the divergent validity of 4 of the subtests of the Mini-Mental State Examination (MMSE): attention, naming, memory, and copy. METHODS: Participants included 126 memory-impaired individuals (mean age, 74 years). Because the naming subtest showed no variability, we did not analyze it further. RESULTS: The convergent validity of the attention, memory, and copy subtests was confirmed with Spearman rank correlation coefficient. Each MMSE subtest was significantly related to a parallel neuropsychological test. We measured divergent validity by testing the difference between the MMSE subtest correlation with its parallel neuropsychological test and its nonparallel neuropsychological test. The MMSE subtests of attention and memory showed similar relationships with their parallel neuropsychological tests as they did with nonparallel neuropsychological tests of attention, memory, and naming. These 2 subtests, however, did show divergence from a neuropsychological test of copy, most likely indicating that these 2 MMSE subtests are measuring the verbal (and not the performance) domain. The MMSE subtest of copy showed the poorest convergent and divergent validity. CONCLUSIONS: The 3 subtests did not show sufficient divergent validity to warrant a conclusion of their domain specificity. Thus, when a more detailed diagnostic profile is required, a thorough neuropsychological evaluation will provide a more valid description of an individual's cognitive profile.
Aged↗
International variation in ophthalmologic management of patients with cataracts. Results from the International Cataract Surgery Outcomes Study.
OBJECTIVES: To describe international variation in the management of patients with cataacts in 4 health care systems and to discuss the potential implications for cost and utilization of services. DESIGN: To characterize current clinical practice on patients with no coexisting medical or ocular conditions, a standardized questionnaire was sent to random samples of ophthalmologists in the United States (response rate, 82.5%), Canada (66.9%), and Barcelona, Spain (70.4%), and to all ophthalmologists in Denmark (80.1%). From the United States, 526 ophthalmologists who performed cataract surgery participated in the study; there were 276 from Canada, 89 from Barcelona, and 82 from Denmark. RESULTS: Although in all 4 sites most surgeons reported that they performed A-scanning, fundus examination, and refraction routinely before surgery, significant crossnational variation was observed in preoperative ophthalmic and medical testing. While preoperative medical tests were virtually unused in Denmark, they were widely used in the other sites. A significantly higher proportion of the surgeons in the United States and Barcelona reported that they performed less than 100 extractions per year compared with surgeons in Canada and Denmark (P < .001). A significantly higher proportion of the surgeons in the United States and Canada were performing predominantly phacoextraction compared with surgeons in Denmark and Barcelona (P < .001). Both within and across sites, considerable variation in number of follow-up visits and postoperative tests was observed. CONCLUSIONS: Significant international variation in the management of healthy patients with cataracts has been observed. If less intensive care is not associated with poorer outcomes, there is the potential for less costly care of patients with cataracts. Further research identifying the most cost-effective practices is needed.
Adult↗
International variation in anesthesia care during cataract surgery: results from the International Cataract Surgery Outcomes Study.
OBJECTIVES: To describe international variation in anesthesia care and monitoring during cataract surgery and to discuss its implications for cost and safety. METHODS: A standardized questionnaire was sent to random samples of ophthalmologists in the United States, Canada, and Barcelona, Spain, and to all ophthalmologists in Denmark. The survey was conducted in 1993 and 1994. Certified ophthalmologists who had performed 1 or more cataract extractions in the previous year were eligible for enrollment. RESULTS: The response rates were 62% in the United States (n=148), 67% in Canada (n=276), 70% in Barcelona (n=89), and 80% in Denmark (n=82). The anesthetic technique for cataract surgery varied significantly between sites (P<.001). Surgeons reported that retrobulbar blocks were used for 46% of the cataract extractions in the United States, 70% in Canada, 66% in Denmark, and 31% in Barcelona. In Barcelona, general anesthesia was used for 23% of the cataract extractions; it was used for less than 3% of the extractions at the other 3 sites. Peribulbar blocks or topical anesthesia was used for the remaining extractions. In the United States, Canada, and Barcelona, surgeons reported that vital functions were monitored during more than 97% of the extractions and anesthesia surveillance was used during more than 78% of the extractions. In Denmark, ophthalmologists reported that vital functions were monitored and anesthesia surveillance was used for 1% of the cataract extractions (P<.001). CONCLUSIONS: Substantial international variation in anesthesia care and monitoring during cataract surgery was observed. The findings suggest a need for further research to determine whether less intensive monitoring is cost-effective.
Anesthesia↗
International applicability of the VF-14. An index of visual function in patients with cataracts.
PURPOSE: There is increased recognition that a rigorous approach to functional assessment should complement the assessment of clinical status. The authors compare the reliability, validity, and responsiveness to clinical change of a visual function index (VF-14) in non-U.S. and in U.S. patients with cataracts. DESIGN: An observational longitudinal study was performed. PARTICIPANTS: One thousand four hundred seven first eye cataract surgery patients were recruited in four international sites: Manitoba (Canada), Denmark, Barcelona (Spain), and the United States. INTERVENTION: Patients were evaluated before cataract surgery and at a 4-month postoperative follow-up visit. Patients completed the preoperative interview and the clinical examination (766 in the United States, 152 in Manitoba, 291 in Denmark, and 198 in Barcelona), and 91.3% of those (1284) also completed the 4-month postoperative follow-up interview and were evaluated postoperatively by an ophthalmologist. MAIN OUTCOME MEASURES: The authors used the following measures: the visual function index (VF-14), the Sickness Impact Profile (SIP), global measures of patients' trouble and satisfaction with vision, and best-corrected visual acuity (VA) in each eye. RESULTS: The VF-14 showed a high internal consistency reliability level in all sites (Cronbach's alpha coefficients > or = 0.84). Correlation of preoperative visual function index scores with the Vision-Related SIP was strong (r = -0.68 in non-U.S. and r = -0.57 in U.S. patients) and with VA in the eye with better vision was moderate (r = 0.40 and r = 0.27, respectively), the pattern of relationships being very similar among U.S. and non-U.S. patients. In patients with only first-eye surgery who reported that their initial trouble with vision had improved, the amount of change in visual function as assessed by the VF-14 (effect size) was large (1.01 for the non-U.S. patients and 1.17 for the U.S. patients). CONCLUSIONS: The non-U.S. versions of the visual function index (VF-14) analyzed are as reliable, valid, and responsive to clinical change as the original U.S. version. These versions are appropriate for international studies of cataract patients outcomes and possibly in routine clinical practice.
Aged↗
Patients' acceptance of waiting for cataract surgery: what makes a wait too long?
The patient's perspective about waiting for elective surgery is an important consideration in the management of waiting lists, yet it has received little attention to date. This study was undertaken to assess the acceptability of personal waiting times from the perspective of patients, and to examine waiting time and patient characteristics associated with the perception that a wait for cataract surgery is too long. The international prospective study was conducted in three sites with explicit waiting systems: Manitoba, Canada; Denmark; and Barcelona, Spain. Patients over the age of 50 years were recruited consecutively from ophthalmologists' practices at the time of their enlistment for first-eye cataract surgery. Anticipated waiting time, opinions about personal waiting time, and patients' visual and health characteristics were identified by means of telephone interviews. The 550 patients interviewed at the time of enlistment for surgery anticipated waits varying from < 1 to 24 months. Clinical visual acuity measures were obtained from patients' ophthalmologists/cataract surgeons. Results indicated that anticipated waiting time was the strongest predictor of patients' tolerance of waiting for cataract surgery. Patient dissatisfaction increased with the duration of the anticipated wait. Patients in all three sites were accepting of waits of three months or less, and considered waits exceeding six months to be excessive. Response to waits between three and six months varied across study sites. Patients with low tolerance for waiting had greater self-reported difficulty with vision, as assessed by a Cataract Symptom Score and expressed trouble with vision. Patients' acceptance of waiting was not associated with clinical visual acuity measures or socio-demographic characteristics. The patient perspective on acceptability of waiting times for cataract surgery suggests that restricting waiting times to less than six months and preferably less than three months and utilizing self-reported measures of visual difficulty in prioritizing patients may contribute to improved management of waiting systems. Patients are more tolerant of their personal waiting times than responses to questions about waiting for elective surgery in general would indicate, and appear to accept waiting times that are longer than those identified as reasonable by specialists.
Aged↗
Practices associated with cataract surgery in Canada: results of a national survey.
OBJECTIVE: To examine Canadian ophthalmologists' reported practices related to cataract surgery. DESIGN: Mailed questionnaire survey. SETTING: Canada. PARTICIPANTS: Random sample of 698 ophthalmologists from the mailing list of the Canadian Ophthalmological Society. Of the 528 eligible ophthalmologists 353 completed the questionnaire (response rate 67%). A total of 276 respondents were classified as cataract surgeons (performed at least one cataract operation in the preceding year [1992]) and were included in the study. OUTCOME MEASURES: Reported use of preoperative ophthalmic tests, surgical technique, cataract anesthesia (including type of block and who administers it) and postoperative care. RESULTS: Most of the preoperative tests examined either were so routine as to be done in almost all cases or were rarely done at all. A total of 52% of the respondents were identified as predominantly extracapsular cataract extraction surgeons (ECCE), 46% as predominantly phacoemulsification surgeons and 2% as predominantly intracapsular cataract extraction surgeons. Overall, 57% of the respondents reported high use of retrobulbar anesthesia, 18% reported high use of peribulbar anesthesia, and 0.7% reported high use of general anesthesia. The mean number of postoperative visits in the first 4 months after surgery was 4.25. The mean rate of Nd:YAG laser capsulotomy in the first year after cataract surgery was 17.9%; 91% of the respondents reported a rate less than 40%. CONCLUSIONS: There seems to be limited use of nonessential preoperative ocular testing by Canadian cataract surgeons. Although ECCE remains the most common type of surgery performed, there appears to be a substantial number of surgeons trying phacoemulsification, and this will likely become the predominant technique in the near future. The self-reported practices of Canadian surgeons with relation to preoperative testing and postoperative follow-up appear to be consistent with the Clinical Practice Guideline for cataract surgery set by the US Agency for Health Care Policy and Research. However, variations in the number of postoperative visits and Nd:YAG capsulotomy rates merit further investigation.
Anesthesia, Local↗
Differential distribution of gamma-aminobutyric acidA receptor subunit (alpha 1, alpha 2, alpha 3, alpha 5 and beta 2 + 3) immunoreactivity in the medial prefrontal cortex of the rat.
A detailed mapping of the gamma-aminobutyric acid (GABA)A receptor subunits (alpha 1, alpha 2, alpha 3, alpha 5 and beta 2 + 3) in the infralimbic/ventral prelimbic region (IL/vPL) of the rat frontal cortex was carried out using subunit-specific antibodies. The alpha 1 and beta 2 + 3 subunit antibodies immunostained all layers of the IL/vPL region. Layers II and III displayed immunostaining of cell bodies whereas I, V and VI showed predominantly neuropil staining. The size of the alpha 1-positive cell bodies corresponded to that of small interneurons (range, 20-55 microns2; mean +/- SEM, 37 +/- 5.5 microns2) as well as pyramidal cells or large interneurons (range, 87-135 microns2; mean +/- SEM, 103.4 +/- 9.7 microns2). However, beta 2 + 3 antibody immunostained only small cell bodies. Immunoreactivity for alpha 2 was restricted to layers I and II, whereas alpha 3 and alpha 5 subunit expression was seen only in layer VI. The antibody to the alpha 2 subunit immunostained small cell bodies (range, 29-63 microns2; mean +/- SEM, 32 +/- 4.5 microns2) in layer II, resembling interneurons. Conversely, both alpha 3 and alpha 5 antibodies immunostained large cell bodies (range, 94-151 microns2; mean +/- SEM, 115.7 +/- 13.4 microns2), consistent with pyramidal cell labelling in layer VI.
Animals↗
Induction of apolipoprotein E mRNA in the hippocampus of the gerbil after transient global ischemia.
B/A4 is the major component of brain amyloid plaque, one of the hallmarks of Alzheimer's disease (AD). B/A4 is a product of proteolytic processing of its precursor, the Alzheimer amyloid precursor protein (APP). Recently, apolipoprotein E (APO-E) has also been shown to be associated with Alzheimer's disease pathology because it is localized to plaques and tangles, and the gene encoding one of the isoforms of APO-E (E4) is associated with late-onset familial and sporadic AD. In addition, APO-E exhibits high affinity for binding to the B-peptide (B/A4). In this study, we have investigated changes in the steady state levels of APP, APO-E, and the astrocyte-specific marker, glial fibrillary acidic protein (GFAP) mRNA in the gerbil hippocampal CA1 region after a 10-min period of bilateral carotid occlusion-induced forebrain ischemia. Following this insult, we observed a loss of 90% of the CA1 neurons by 72 h post-ischemia. The mRNA levels on day 1 through day 7 post-ischemia were quantitated using an image analyzer. There was an increase in the transcription of APO-E and GFAP mRNAs, with the levels of APO-E mRNA being the highest (3-fold increase on day 7 post-ischemia) (P < 0.005). However, we did not see an increase in APP mRNA. In a parallel study [Hall, E.D. et al., Exp. Neurol., 135(1995) 17-27], we have also seen an increase in levels of APO-E and GFAP protein measured by immunocytochemistry. However, in contrast to the lack of an increase in APP mRNA, immunocytochemical measurement of APP did show an increase, perhaps due to delayed translation of previously formed mRNA. We suggest that neuronal injury or insult results in the induction of certain genes (and, therefore, protein synthesis) in the surrounding reactive astrocytes, and these proteins may contribute to post-injury amyloidogenesis.
Amyloid beta-Protein Precursor↗