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Christopher Randolph

Publications and source records attributed to Christopher Randolph.

12 recordsLinked to original sources
PubMed2006

A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1.

To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on 2 separate protocols. Using log-rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival (training set: hazard ratio [HR], 5.16; P < .001; test cohort: HR, 4.75; P < .001). The high-risk score also was an independent predictor of outcome endpoints in multivariate analysis (P < .001) that included the International Staging System and high-risk translocations. In a comparison of paired baseline and relapse samples, the high-risk score frequency rose to 76% at relapse and predicted short postrelapse survival (P < .05). Multivariate discriminant analysis revealed that a 17-gene subset could predict outcome as well as the 70-gene model. Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.

Aged↗
PubMed2005

Standard regression-based methods for measuring recovery after sport-related concussion.

Clinical decision making about an athlete's return to competition after concussion is hampered by a lack of systematic methods to measure recovery. We applied standard regression-based methods to statistically measure individual rates of impairment at several time points after concussion in college football players. Postconcussive symptoms, cognitive functioning, and balance were assessed in 94 players with concussion (based on American Academy of Neurology Criteria) and 56 noninjured controls during preseason baseline testing, and immediately, 3 hr, and 1, 2, 3, 5, and 7 days postinjury. Ninety-five percent of injured players exhibited acute concussion symptoms and impairment on cognitive or balance testing immediately after injury, which diminished to 4% who reported elevated symptoms on postinjury day 7. In addition, a small but clinically significant percentage of players who reported being symptom free by day 2 continued to be classified as impaired on the basis of objective balance and cognitive testing. These data suggest that neuropsychological testing may be of incremental utility to subjective symptom checklists in identifying the residual effects of sport-related concussion. The implementation of neuropsychological testing to detect subtle cognitive impairment is most useful once postconcussive symptoms have resolved. This management model is also supported by practical and other methodological considerations.

Acute Disease↗
PubMed2005

Association between recurrent concussion and late-life cognitive impairment in retired professional football players.

OBJECTIVE: Cerebral concussion is common in collision sports such as football, yet the chronic neurological effects of recurrent concussion are not well understood. The purpose of our study was to investigate the association between previous head injury and the likelihood of developing mild cognitive impairment (MCI) and Alzheimer's disease in a unique group of retired professional football players with previous head injury exposure. METHODS: A general health questionnaire was completed by 2552 retired professional football players with an average age of 53.8 (+/-13.4) years and an average professional football playing career of 6.6 (+/- 3.6) years. A second questionnaire focusing on memory and issues related to MCI was then completed by a subset of 758 retired professional football players (> or = 50 yr of age). Results on MCI were then cross-tabulated with results from the original health questionnaire for this subset of older retirees. RESULTS: Of the former players, 61% sustained at least one concussion during their professional football career, and 24% sustained three or more concussions. Statistical analysis of the data identified an association between recurrent concussion and clinically diagnosed MCI (chi = 7.82, df = 2, P = 0.02) and self-reported significant memory impairments (chi = 19.75, df = 2, P = 0.001). Retired players with three or more reported concussions had a fivefold prevalence of MCI diagnosis and a threefold prevalence of reported significant memory problems compared with retirees without a history of concussion. Although there was not an association between recurrent concussion and Alzheimer's disease, we observed an earlier onset of Alzheimer's disease in the retirees than in the general American male population. CONCLUSION: Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.

Adult↗
PubMed2004

Complement C7 deficiency presenting as recurrent aseptic meningitis.

BACKGROUND: Complement deficiency states are rare inherited disorders that may predispose affected individuals to angioedema, collagen vascular disease, or infection due to encapsulated organisms, especially Neisseria meningitidis. OBJECTIVES: To report the case of a 36-year-old man of Irish descent with recurrent culture-negative neutrophilic meningitis, to offer potential reasons for the inability to recover a causative pathogen, and to review the genetics and prevalence of complement deficiency states, the methods of screening for such deficiencies, the features of meningococcal infection as they relate to such deficiencies, and management strategies for clinicians caring for patients with such deficiencies. METHODS: The patient presented in 1988 and again in 2002 with culture-negative neutrophilic meningitis. His second episode was characterized by a rash suggestive of meningococcal infection, prompting immunologic evaluation. RESULTS: Immunologic evaluation revealed an undetectable CH50 level. Levels of C1, C2, and C5 through C9 were normal except for C7, which was undetectable. Further testing revealed that the patient's sister was also C7 deficient. CONCLUSIONS: Complement component deficiencies are relatively rare; individuals with collagen vascular disease and systemic neisserial infection should be screened using either the CH50 or the APH-50 assay. Key to the management of a late-complement component-deficient host is counseling, education about meningococcal infection, and discussions about the potential benefits of chemoprophylaxis and immunoprophylaxis. The ability to detect the bacterial cause of meningitis in such patients is organism dependent and may be influenced by factors such as cerebrospinal fluid bacterial concentration and previous antibiotic drug exposure.

Adult↗
PubMed2003

Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study.

CONTEXT: Approximately 300 000 sport-related concussions occur annually in the United States, and the likelihood of serious sequelae may increase with repeated head injury. OBJECTIVE: To estimate the incidence of concussion and time to recovery after concussion in collegiate football players. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 2905 football players from 25 US colleges were tested at preseason baseline in 1999, 2000, and 2001 on a variety of measures and followed up prospectively to ascertain concussion occurrence. Players injured with a concussion were monitored until their concussion symptoms resolved and were followed up for repeat concussions until completion of their collegiate football career or until the end of the 2001 football season. MAIN OUTCOME MEASURES: Incidence of concussion and repeat concussion; type and duration of symptoms and course of recovery among players who were injured with a concussion during the seasons. RESULTS: During follow-up of 4251 player-seasons, 184 players (6.3%) had a concussion, and 12 (6.5%) of these players had a repeat concussion within the same season. There was an association between reported number of previous concussions and likelihood of incident concussion. Players reporting a history of 3 or more previous concussions were 3.0 (95% confidence interval, 1.6-5.6) times more likely to have an incident concussion than players with no concussion history. Headache was the most commonly reported symptom at the time of injury (85.2%), and mean overall symptom duration was 82 hours. Slowed recovery was associated with a history of multiple previous concussions (30.0% of those with > or =3 previous concussions had symptoms lasting >1 week compared with 14.6% of those with 1 previous concussion). Of the 12 incident within-season repeat concussions, 11 (91.7%) occurred within 10 days of the first injury, and 9 (75.0%) occurred within 7 days of the first injury. CONCLUSIONS: Our study suggests that players with a history of previous concussions are more likely to have future concussive injuries than those with no history; 1 in 15 players with a concussion may have additional concussions in the same playing season; and previous concussions may be associated with slower recovery of neurological function.

Adolescent↗
PubMed2003

Acute effects and recovery time following concussion in collegiate football players: the NCAA Concussion Study.

CONTEXT: Lack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury. OBJECTIVE: To prospectively measure immediate effects and natural recovery course relating to symptoms, cognitive functioning, and postural stability following sport-related concussion. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1631 football players from 15 US colleges. All players underwent preseason baseline testing on concussion assessment measures in 1999, 2000, and 2001. Ninety-four players with concussion (based on American Academy of Neurology criteria) and 56 noninjured controls underwent assessment of symptoms, cognitive functioning, and postural stability immediately, 3 hours, and 1, 2, 3, 5, 7, and 90 days after injury. MAIN OUTCOME MEASURES: Scores on the Graded Symptom Checklist (GSC), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and a neuropsychological test battery. RESULTS: No player with concussion was excluded from participation; 79 players with concussion (84%) completed the protocol through day 90. Players with concussion exhibited more severe symptoms (mean GSC score 20.93 [95% confidence interval [CI], 15.65-26.21] points higher than that of controls), cognitive impairment (mean SAC score 2.94 [95% CI, 1.50-4.38] points lower than that of controls), and balance problems (mean BESS score 5.81 [95% CI, -0.67 to 12.30] points higher than that of controls) immediately after concussion. On average, symptoms gradually resolved by day 7 (GSC mean difference, 0.33; 95% CI, -1.41 to 2.06), cognitive functioning improved to baseline levels within 5 to 7 days (day 7 SAC mean difference, -0.03; 95% CI, -1.33 to 1.26), and balance deficits dissipated within 3 to 5 days after injury (day 5 BESS mean difference, -0.31; 95% CI, -3.02 to 2.40). Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7. There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion. CONCLUSIONS: Collegiate football players may require several days for recovery of symptoms, cognitive dysfunction, and postural instability after concussion. Further research is required to determine factors that predict variability in recovery time after concussion. Standardized measurement of postconcussive symptoms, cognitive functioning, and postural stability may enhance clinical management of athletes recovering from concussion.

Acute Disease↗
PubMed2002

Neuropsychological testing: evolution and emerging trends.

Neuropsychological (NP) test batteries have evolved as an amalgam of intelligence tests, various individual measures of "biological" cognition, and sensory and motor testing. The early emphasis of NP testing was to identify "organicity" and central nervous system lesion localization. More recent approaches have emphasized the profiling of performance across individual neurocognitive domains (eg, attention, memory, and language) to facilitate diagnosis and treatment planning. However, the field is still hampered by the use of many tests that are antiquated, excessively long, or of dubious psychometric quality. Some of these problems may have contributed to the current under-utilization of NP testing in diagnostic workups of neuropsychiatric disorders. This paper reviews some of the recent changes in the field that hold promise for substantially shortening assessments, improving diagnostic reliability, and making NP testing more cost-effective and practical.

Journal Article↗
PubMed2002

Immediate neurocognitive effects of concussion.

OBJECTIVE: To prospectively measure the immediate neurocognitive effects and early course of recovery from concussion and to examine the effects of loss of consciousness (LOC) and posttraumatic amnesia (PTA) on the severity of neurocognitive impairment immediately after concussion. METHODS: A sports-related concussion research model was used to allow prospective immediate evaluation of concussion. A total of 2385 high school and college football players were studied. Ninety-one players (3.8%) sustained concussions during the study. A brief neurocognitive and neurological screening measure, the Standardized Assessment of Concussion, was used to assess cognitive functioning before the football season, immediately after injury, and 15 minutes, 48 hours, and 90 days after injury. RESULTS: Standardized Assessment of Concussion scores immediately after concussion were significantly lower than the preseason baseline score and the noninjured population baseline mean, even for injured subjects without LOC or PTA. Subjects with LOC were most severely impaired immediately after injury, whereas those without LOC or PTA were least impaired. Significant impairment was also detected 15 minutes after injury, but all three groups returned to baseline levels of cognitive functioning within 48 hours. CONCLUSION: These findings are the first to demonstrate not only that a gradient of increasing concussion severity is represented by PTA and LOC but also that measurable neurocognitive abnormalities are evident immediately after injury without PTA or LOC.

Adolescent↗
PubMed2002

Test-retest stability of the Repeatable Battery for the Assessment of Neuropsychological Status in schizophrenia.

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was designed as a cognitive screening test, providing both a total scale score and five specific cognitive ability index scores. This study examined the test-retest stability of the RBANS in individual patients with schizophrenia relative to a healthy comparison group. METHOD: A total of 181 patients with schizophrenia or schizoaffective disorder were recruited from three clinical settings. Healthy comparison subjects were recruited as part of the RBANS standardization. Participants were administered one form of the RBANS on one occasion and another form at a later date, with intervals ranging from 1 to 134 days. RESULTS: Intraclass correlation coefficients for the RBANS total scale were 0.84 for the patients with schizophrenia and 0.77 for the healthy comparison subjects. Confidence intervals and percentile data for the total scale change scores were similar for both groups. CONCLUSIONS: The RBANS demonstrated reasonable intraclass correlation coefficient test-retest reliability for both schizophrenia patients and healthy comparison subjects. Confidence intervals are comparable to those previously published for the WAIS-R and Wechsler Memory Scale-Revised, suggesting that retest measurement error is not dramatically increased in the RBANS, despite the brevity of the test. These data may serve as an informative guide for using the RBANS to evaluate neuropsychological change on the level of the individual subject.

Adolescent↗
PubMed2001

Implementation of Neuropsychological Testing Models for the High School, Collegiate, and Professional Sport Settings.

OBJECTIVE: To review models for the use of neuropsychological testing in the management of sport-related concussion at various levels of competition. BACKGROUND: As we come to understand the natural history of sport-related concussive brain injury, it is increasingly evident that significant neurologic risks are associated with this type of injury. These risks include (1) acute intracranial pathology, (2) catastrophic brain swelling from second-impact syndrome, and (3) the potential risk for markedly prolonged recovery or permanent cognitive dysfunction associated with multiple concussions. DESCRIPTION: Neuropsychological testing has proved to be a useful tool in the medical management of sport-related concussion. In this paper, I describe a systematic model for the implementation of neuropsychological assessment of athletes at various levels of competition. CLINICAL ADVANTAGES: The systematic model was designed to incorporate state-of-the-art techniques for the detection and tracking of neurocognitive deficits associated with concussion into recently formulated guidelines for the medical management of sport-related concussion. Current applications of the model are discussed, as well as ongoing studies designed to elaborate the empirical underpinnings of the model and refine clinical decision making in this area.

Journal Article↗
PubMedDate not supplied

Is neuropsychological testing useful in the management of sport-related concussion?

OBJECTIVE: Neuropsychological (NP) testing has been used for several years as a way of detecting the effects of sport-related concussion in order to aid in return-to-play determinations. In addition to standard pencil-and-paper tests, computerized NP tests are being commercially marketed for this purpose to professional, collegiate, high school, and elementary school programs. However, a number of important questions regarding the clinical validity and utility of these tests remain unanswered, and these questions present serious challenges to the applicability of NP testing for the management of sport-related concussion. Our purpose is to outline the criteria that should be met in order to establish the utility of NP instruments as a tool in the management of sport-related concussion and to review the degree to which existing tests have met these criteria. DATA SOURCES: A comprehensive literature review of MEDLINE and PsychLit from 1990 to 2004, including all prospective, controlled studies of NP testing in sport-related concussion. DATA SYNTHESIS: The effects of concussion on NP test performance are so subtle even during the acute phase of injury (1-3 days postinjury) that they often fail to reach statistical significance in group studies. Thus, this method may lack utility in individual decision making because of a lack of sensitivity. In addition, most of these tests fail to meet other psychometric criteria (eg, adequate reliability) necessary for this purpose. Finally, it is unclear that NP testing can detect impairment in players once concussion-related symptoms (eg, headache) have resolved. Because no current guideline for the management of sport-related concussion allows a symptomatic player to return to sport, the incremental utility of NP testing remains questionable. CONCLUSIONS/RECOMMENDATIONS: Despite the theoretic rationale for the use of NP testing in the management of sport-related concussion, no NP tests have met the necessary criteria to support a clinical application at this time. Additional research is necessary to establish the utility of these tests before they can be considered part of a routine standard of care, and concussion recovery should be monitored via the standard clinical examination and subjective symptom checklists until NP testing or other methods are proven effective for this purpose.

Journal Article↗