Impact of early intervention on outcome following mild head injury in adults.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A M Salazar
Publications and source records attributed to A M Salazar.
Progesterone receptor isoforms expression in the prepuberal and adult male rat brain.
Progesterone receptor (PR) isoforms expression was determined in several regions of the prepuberal and adult male rat brain by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10-h light-dark cycle, with lights on at 0600 h were used. We found that in the hypothalamus of prepuberal animals the expression of both PR isoforms was similar, whereas PR-A expression was higher than that of PR-B in adults. In the cerebellum PR-B expression was predominant in both prepuberal and adult rats. In both ages PR-A and PR-B exhibited a non-significant tendency to be predominant in the hippocampus and the preoptic area respectively. In the frontal cortex and the olfactory bulb PR isoforms were expressed at a similar level. These results indicate a differential expression pattern of PR isoforms in the male rat brain and suggest that the tissue-specific expression of PR-A and PR-B is important for the appropriate response of each cerebral region to progesterone.
Age Factors↗
Patterns of verbal learning and memory in traumatic brain injury.
CVLT and WMS-R Digit Span variables were used to calculate indexes of seven specific short- and long-term memory processes: working memory span and central executive functions, and long-term memory encoding, consolidation, retention, retrieval, control abilities. Scores on these indexes were then cluster-analyzed to determine whether subtypes of memory performance exist that correspond to deficits in these theoretical memory constructs. Parallel analyses were conducted with two large samples (N = 150 and N = 151) of individuals who had sustained a traumatic brain injury (TBI). Findings showed that TBI results in subgroups of memory disorders with specific deficits in consolidation, retention, and retrieval processes. Control problems (keeping track of list versus non-list items) only appeared in conjunction with retrieval deficits. Working memory span and central executive functioning (i.e., the ability to manipulate information in working memory) do not appear to be deficits characteristic of TBI as no such clusters emerged in the analyses. By using specific indexes of memory processes, and in contrast to previous studies, patterns of memory dysfunction were found that correspond to deficits in theoretically meaningful memory constructs.
Adult↗
Biased responding: a case series demonstrating a relationship between somatic symptoms and impaired recognition memory performance for traumatic brain injured individuals.
Biased responding on the Sternberg Recognition Memory Test was observed in four patients with traumatic brain injury. None of these individuals met the Diagnostic and Statistical Manual's (DSM-IV) criteria for malingering. Individual recognition memory scores were high shortly after injury, declined to chance or below at the 6- and 12-month evaluations, and then showed substantial recovery by the 24-month evaluation. Recall memory performance actually declined slightly across this same 2-year period. Recognition memory scores were related to the extent to which the patients endorsed somatic items on the Hamilton Rating Scale for Depression (HAM-D). Poor performance was associated with high somatic scores. The relationship between memory and somatic scores on the HAM-D in this case series suggests that unconscious processes can influence memory performance and, because of this, that clinicians should not use such performance as a primary indicator of malingering. More importantly, biased responding and actual memory deficits may coexist. This is indicated in the current cases by the failure of recall memory to improve during the 2 years these patients were followed.
Adult↗
ATM status confers sensitivity to arsenic cytotoxic effects.
Arsenic (As), a human carcinogen, represents a worldwide health problem due to the high number of people exposed to this element in their drinking water. Previously our group has demonstrated that As can impair lymphocyte cell proliferation in vitro and in vivo and can increase the level of P53 protein, with different responses to these effects between individuals. Recently it has been shown that ATM protein, responsible for the autosomal recessive disorder ataxia telangiectasia (AT), regulates P53. In this study the induced response of P53 was evaluated following exposure to As in human lymphoblastoid cell lines normal (+/+), heterozygous (+/-) or homozygous (-/-) for the mutant ATM gene. After 24 h As treatment we found a dose-dependent induction of P53 in normal and heterozygous cell lines, although differences between cell lines were observed. An increase in P21(WAF) protein, a main effector of P53 activation, was also observed in the same cell lines. In contrast, neither P53 nor P21 induction was detected in homozygous cells. The ATM (+/-) and (-/-) genotypes confer more sensitivity to As cytotoxic effects than the normal allelic condition. Paradoxically, ATM heterozygous cells were more sensitive to As, leading us to propose that this might be related to activation of apoptosis and removal of non-repairable cells. In contrast, in AT cells in which ATM is absent or mutated activation of P53 and its target genes is abrogated, allowing cells to replicate with damage in the presence of As, with cell death ensuing by a pathway different from P53.
Arsenic↗
Simian virus 40 Vp1 DNA-binding domain is functionally separable from the overlapping nuclear localization signal and is required for effective virion formation and full viability.
A DNA-binding domain (DBD) was identified on simian virus 40 (SV40) major capsid protein Vp1, and the domain's function in the SV40 life cycle was examined. The DBD was mapped by assaying various recombinant Vp1 proteins for DNA binding in vitro. The carboxy-terminal 58-residue truncated Vp1DeltaC58 pentamer bound DNA with a K(d) of 1.8 x 10(-9) M in terms of the protein pentamer, while full-length Vp1 and carboxy-terminal-17-truncated Vp1DeltaC17 had comparable apparent K(d)s of 5.3 x 10(-9) to 7.3 x 10(-9) M in terms of the protein monomers. Previously identified on Vp1 was a nuclear localization signal (NLS) consisting of two N-terminal basic clusters, NLS1 (4-KRK-6) and NLS2 (15-KKPK-18). Vp1DeltaC58 pentamers harboring multiple-point mutations in NLS1 (NLSm1), NLS2 (NLSm2), or both basic clusters (NLSm1. 2) had progressively decreased DNA-binding activity, down to 0.7% of the Vp1DeltaC58 level for NLSm1. 2 Vp1. These data, along with those of N-terminally truncated proteins, placed the DBD in overlap with the bipartite NLS. The role of the Vp1 DBD during infection was investigated by taking advantage of NLS phenotypic complementation (N. Ishii, A. Nakanishi, M. Yamada, M. H. Macalalad, and H. Kasamatsu, J. Virol. 68:8209-8216, 1994), in which an NLS-defective Vp1 could localize to the nucleus in the presence of wild-type minor capsid proteins Vp2 and Vp3. This approach made it possible to dissect the role of the bifunctional Vp1 NLS-DBD in virion assembly in the nucleus. Mutants of the viable nonoverlapping SV40 (NO-SV40) DNA NLSm1, NLSm2, and NLSm1. 2 replicated normally following transfection into host cells and produced capsid proteins at normal levels. All mutant Vp1s were able to interact with Vp3 in vitro. The mutants NLSm1 and NLSm1. 2 were nonviable, and the mutant Vp1s unexpectedly failed to localize to the nucleus though Vp2 and Vp3 did, suggesting that the mutated NLS1 acted as a dominant signal for the cytoplasmic localization of Vp1. Mutant NLSm2, for which the mutant Vp1's nuclear localization defect was complemented by Vp2 and Vp3, displayed a 5,000-fold reduced viability. Analysis of NLSm2 DNA-transfected cell lysate revealed a 10-fold reduction in the level of DNase I-protected viral DNA, and yet virion-like particles were found among the DNase I-resistant material. Collective results support a role for Vp1 NLS2-DBD2 in the assembly of virion particles. The results also suggest that this determinant can function in the infection of new cells.
Animals↗
An EEG severity index of traumatic brain injury.
EEG spectral analyses were conducted from 19 scalp locations for patients with mild (n=40), moderate (n=25), and severe (n=43) traumatic brain injury (TBI), 15 days to 4 years after injury. Severity of TBI was judged by emergency hospital admission records (Glasgow Coma Score and duration of coma and amnesia). Highest-loading EEG variables on each factor that differed significantly between severe and mild TBI by univariate t-test were entered into a multivariate discriminant analysis, yielding 16 variables. Discriminant analysis between mild and severe TBI groups showed classification accuracy of 96.39%, sensitivity 95.45%, and specificity 97.44%. The EEG discriminant score also measured intermediate severity in moderate TBI patients. Results were cross-validated in 503 VA patients. Significant correlations between EEG discriminant scores, emergency admission measures, and post-trauma neuropsychological test scores validated the discriminant function as an index of severity of injury and a classifier of the extremes of severity.
Adolescent↗
CT of in situ vascular stump thrombosis after pulmonary resection for cancer.
Explore the source record for details and available documents.
Adenocarcinoma↗
Bronchial atresia with relapsing pulmonary infection in a middle-aged man.
Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.
Activities of Daily Living↗
Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. 1997.
Explore the source record for details and available documents.
Clinical Trials, Phase III as Topic↗
A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.
BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.
Adjuvants, Immunologic↗
Cognitive rehabilitation for traumatic brain injury: A randomized trial. Defense and Veterans Head Injury Program (DVHIP) Study Group.
CONTEXT: Traumatic brain injury (TBI) is a principal cause of death and disability in young adults. Rehabilitation for TBI has not received the same level of scientific scrutiny for efficacy and cost-efficiency that is expected in other medical fields. OBJECTIVE: To evaluate the efficacy of inpatient cognitive rehabilitation for patients with TBI. DESIGN AND SETTING: Single-center, parallel-group, randomized trial conducted from January 1992 through February 1997 at a US military medical referral center. PATIENTS: One hundred twenty active-duty military personnel who had sustained a moderate-to-severe closed head injury, manifested by a Glasgow Coma Scale score of 13 or less, or posttraumatic amnesia lasting at least 24 hours, or focal cerebral contusion or hemorrhage on computed tomography or magnetic resonance imaging. INTERVENTIONS: Patients were randomly assigned to an intensive, standardized, 8-week, in-hospital cognitive rehabilitation program (n=67) or a limited home rehabilitation program with weekly telephone support from a psychiatric nurse (n=53). MAIN OUTCOME MEASURES: Return to gainful employment and fitness for military duty at 1-year follow-up, compared by intervention group. RESULTS: At 1-year follow-up, there was no significant difference between patients who had received the intensive in-hospital cognitive rehabilitation program vs the limited home rehabilitation program in return to employment (90% vs 94%, respectively; P=.51; difference, 4% [95% confidence interval ¿CI¿, -5% to 14%]) or fitness for duty (73% vs 66%, respectively; P=. 43; difference, 7% [95% CI, -10% to 24%]). There also were no significant differences in cognitive, behavioral, or quality-of-life measures. In a post-hoc subset analysis of patients who were unconscious for more than 1 hour (n = 75) following TBI, the in-hospital group had a greater return-to-duty rate (80% vs 58%; P=. 05). CONCLUSIONS: In this study, the overall benefit of in-hospital cognitive rehabilitation for patients with moderate-to-severe TBI was similar to that of home rehabilitation. These findings emphasize the importance of conducting randomized trials to evaluate TBI rehabilitation interventions. JAMA. 2000;283:3075-3081
Absenteeism↗
Defense and Veterans Head Injury Program: background and overview.
Traumatic brain injury (TBI) is the principal cause of death and disability for young Americans, with an estimated societal cost of over $39 billion per year. The Defense and Veterans Head Injury Program (DVHIP) represents a close collaboration among the Departments of Defense (DoD) and Veterans Affairs (DVA), the Brain Injury Association (BIA), and the International Brain Injury Association (IBIA). Its principal mission is to ensure that military and veteran patients with head injury receive TBI-specific evaluation, treatment, rehabilitation, and follow-up, while at the same time addressing the readiness mission of the military and helping to define optimal care for victims of TBI nationwide. Defense and Veterans Head Injury Program activities can be grouped into three broad classes: (1) TBI education, community service, and primary prevention projects; (2) combined TBI clinical treatment, rehabilitation, and clinical research projects; and (3) clinically linked TBI laboratory research projects. It is thus based on a prudent integration of clinical care and follow-up with programmatic clinical and clinically related laboratory research, TBI prevention, and education. This previously nonexistent clinical infrastructure now offers a valuable base for ongoing TBI clinical research.
Animals↗
A home program of rehabilitation for moderately severe traumatic brain injury patients. The DVHIP Study Group.
We have recently reported the results of a prospective controlled randomized trial comparing home versus inpatient cognitive rehabilitation for patients with moderate to severe head injury. That study showed no overall difference in outcomes between the two groups.(1) In this article, we provide further details of the home program arm of the study. All patients in the home program received medical treatment as needed, a multidisciplinary in-hospital evaluation, and TBI counseling before entering the eight-week home program, which then included guidance on home activities, as well as weekly telephone calls from a psychiatric nurse.
Activities of Daily Living↗
Role of simian virus 40 Vp1 cysteines in virion infectivity.
We have developed a new nonoverlapping infectious viral genome (NO-SV40) in order to facilitate structure-based analysis of the simian virus 40 (SV40) life cycle. We first tested the role of cysteine residues in the formation of infectious virions by individually mutating the seven cysteines in the major capsid protein, Vp1. All seven cysteine mutants-C9A, C49A, C87A, C104A, C207S, C254A, and C267L-retained viability. In the crystal structure of SV40, disulfide bridges are formed between certain Cys104 residues on neighboring pentamers. However, our results show that none of these disulfide bonds are required for virion infectivity in culture. We also introduced five different mutations into Cys254, the most strictly conserved cysteine across the polyomavirus family. We found that C254L, C254S, C254G, C254Q, and C254R mutants all showed greatly reduced (around 100,000-fold) plaque-forming ability. These mutants had no apparent defect in viral DNA replication. Mutant Vp1's, as well as wild-type Vp2/3, were mostly localized in the nucleus. Further analysis of the C254L mutant revealed that the mutant Vp1 was able to form pentamers in vitro. DNase I-resistant virion-like particles were present in NO-SV40-C254L-transfected cell lysate, but at about 1/18 the amount in wild-type-transfected lysate. An examination of the three-dimensional structure reveals that Cys254 is buried near the surface of Vp1, so that it cannot form disulfide bonds, and is not involved in intrapentamer interactions, consistent with the normal pentamer formation by the C254L mutant. It is, however, located at a critical junction between three pentamers, on a conserved loop (G2H) that packs against the dual interpentamer Ca(2+)-binding sites and the invading C-terminal helix of an adjacent pentamer. The substitution by the larger side chains is predicted to cause a localized shift in the G2H loop, which may disrupt Ca(2+) ion coordination and the packing of the invading helix, consistent with the defect in virion assembly. Our experimental system thus allows dissection of structure-function relationships during the distinct steps of the SV40 life cycle.
Capsid↗
Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group.
Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon beta-1a (IFNbeta-1a, 30 microg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNbeta-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNbeta-1a group. These results support and extend previous observations of significant beneficial effects of IFNbeta-1a for relapsing MS.
Adolescent↗
A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).
OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.
Adjuvants, Immunologic↗
Cerebrospinal fluid abnormalities in a phase III trial of Avonex (IFNbeta-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.
BACKGROUND AND OBJECTIVE: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo-controlled, double-blind, phase III clinical trial of IFNbeta-Studies supported by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex , Biogen). The clinical trial demonstrated that IFNbeta-1a treatment resulted in significantly reduced disability progression, annual relapse rate, and new brain lesions visualized by cranial magnetic resonance imaging. The objectives of the current study were to determine: (a) whether CSF abnormalities in MS patients correlated with disease or MRI characteristics, and (b) effects of IFNbeta-1a therapy on these CSF abnormalities. METHODS: CSF was analyzed from 262 (87%) of the 301 study subjects at entry into the clinical trial, and a second CSF sample was analyzed from 137 of these 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), IgG index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse rate, gadolinium enhancement, and EDSS change according to baseline CSF status was used to determine the predictive value of CSF for subsequent clinical and MRI disease activity. Change in CSF parameters after 104 weeks were used to determine the effects of treatment. RESULTS: (1) At study baseline, 37% of the subjects had abnormal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chains, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) Baseline IgG index, kappa light chains, and OCB showed weakly positive, statistically significant correlations with Gd-enhanced lesion volume and T2 lesion volume. WBC showed a statistically significant correlation with Gd-enhancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical and MRI disease activity in placebo recipients. (4) IFNbeta-1a treatment resulted in significantly reduced CSF WBC counts, but there was no treatment-related change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. CONCLUSIONS: The current study documents significant reductions in CSF WBC counts in patients treated with IFNbeta-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-treated relapsing MS patients.
Adjuvants, Immunologic↗