An editorial response to Smith-Knapp et al.'s 'Predicting independence from neuropsychological tests following traumatic brain injury'.
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Activities of Daily Living↗
Biomedical subjects
B Johnstone
Publications and source records attributed to B Johnstone.
Extent of intellectual, cognitive, and academic decline in adolescent traumatic brain injury.
Pre-injury cognitive data are rarely available for review for individuals suffering from traumatic brain injury (TBI). Although pre-injury intelligence and academic scores may be available, particularly if an individual is learning-disabled (LD), data on specific cognitive abilities are unlikely to exist. We present neuropsychological data for a 15-year-old Caucasian female with a learning disability who was administered IQ testing 2 weeks prior to a significant TBI, as well as other measures of specific cognitive abilities (e.g. memory and perceptual-motor skills) throughout her education. Comparison of pre- and post-TBI data showed: (1) global and generally consistent decline in all cognitive areas and (2) relatively stable performance on tests of academic ability, supporting the validity of such test scores as estimates of premorbid intelligence.
Adolescent↗
The comparability of the WRAT-R reading test and NAART as estimates of premorbid intelligence in neurologically impaired patients.
A study by Wiens, Bryan, and Crossen (1993) suggests the Wide Range Achievement Test-Revised (WRAT-R) Reading subtest and North American Adult Reading Test (NAART) are adequate predictors of Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores for a normal population. Although it is common practice to use reading scores to estimate premorbid IQ in clinical populations, the WRAT-R and NAART have not been compared using individuals with brain dysfunction. The current study cross-validated the Wiens et al. (1993) study using neurologically impaired populations: traumatic brain injury (n = 118), dementia (n = 37), and other neurologic impairments (n = 77). The results were generally consistent across all three groups: (a) the WRAT-R and NAART were equivalent and accurate estimates of average VIQ levels; (b) the WRAT-R and NAART were equivalent but underestimates of higher intelligence ranges; and (c) the WRAT-R is a more accurate estimate for lower VIQ ranges, although both are overestimates. This third finding is in contrast to Wiens et al.'s (1993) results that suggest the WRAT-R is an accurate estimate of lower IQ ranges for normals. It is concluded that the WRAT-R is the preferred measure of premorbid verbal intelligence for psychometric and clinical reasons.
Journal Article↗
Immunohistochemical analysis of an equine model of synovitis-induced arthritis.
OBJECTIVES: To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone. ANIMALS: 2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2). PROCEDURE: Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articular cartilage sections and attached synovial membrane from the third carpal bones were examined by immunohistochemical distribution of interleukin 1 beta, tumor necrosis factor (TNF)-alpha, TNF receptors (P55, P75) and 3-B-3(-) epitopes, and by localization of proteoglycans (metachromatic staining). Proteoglycan extracts were assessed by metachromatic staining or western blotting and immunohistochemical staining, using anti-3-B- antibodies. RESULTS: Enhanced immunoreactivity for the cytokines and receptors was found in inflamed synovial membrane and noncalcified cartilage (group 2a more than 2b). Metachromasia of the noncalcified cartilage was greater in group-1 than in group-2a and group-2b specimens. In group 2a, chondrocyte hypertrophy and enhanced immunoreactivity for 3-B-3(-) epitope in areas of increased cytokine immunoreactivity suggested possible phenotypic change of the chondrocytes in response to synovitis. Immunohistochemical analysis by western blotting of proteoglycan extracts indicated strong 3-B-3(-) epitope immunolocalization in group-2a, weaker staining in group-2b, and barely detectable stain in group-1 specimens, which correlated with in situ immunolocalization. CONCLUSIONS: Intra-articular administration of LPS may be used to induce a synovial environment conductive to increased immunoreactivity of interleukin 1 beta, TNF-alpha, and its receptors in equine synovial membrane and articular cartilage. These cytokines may be involved in the early phenotypic change of chondrocytes that is believed to occur in osteoarthritis and is characterized in this study by enhanced 3-B-3(-) epitope immunoreactivity and chondrocyte hypertrophy.
Animals↗
The large proteoglycans of the human intervertebral disc. Changes in their biosynthesis and structure with age, topography, and pathology.
STUDY DESIGN: The structure and extracellular assembly of the newly synthesized aggregating proteoglycans of the human intervertebral disc were examined using an explant culture system. OBJECTIVES: The objective was to study the changes with aging, topography, and pathology, comparing newly synthesized with endogenous proteoglycans. SUMMARY OF BACKGROUND DATA: No detailed studies of the biosynthesis of human disc proteoglycans have been previously reported. METHODS: A method of explant culture that minimizes swelling and matrix loss was used to maintain the tissue architecture. Slices of postmortem and pathologic disc tissues were incubated in medium containing polyethylene glycol at appropriate concentrations to balance the swelling pressure of the tissue. The disc slices were contained in small-pore dialysis tubing to prevent penetration of the polyethylene glycol into the tissue. The newly synthesized proteoglycans were radiolabeled with [35S]-sulphate. Proteoglycans were then extracted from the tissue slices and characterized with gel chromatographic and electrophoretic techniques. RESULTS: It was found that a single, high molecular weight proteoglycan is the major 35S-labeled synthesis product of disc cells at all ages. However, biosynthetic changes do occur: the monomer made by fetal and newborn disc cells was larger than that of adults. Furthermore, adult disc cells made other minor large 35S-labeled products, the synthesis pattern of which varied between regions. CONCLUSION: These results provide the first evidence that biosynthetic changes contribute to the age-related increase in the heterogeneity of the human disc proteoglycan population.
Adolescent↗
Osteoarthritis in cynomolgus macaques. II. Detection of modulated proteoglycan epitopes in cartilage and synovial fluid.
The purpose of the present study was to determine the usefulness of the monoclonal antibodies 7-D-4 and 3-B-3 as biomarkers of severity of naturally occurring osteoarthritis in the knee joints of adult cynomolgus macaques. The antibodies were used to immunolocate chondroitin sulfate proteoglycan epitopes in articular cartilage or synovial fluid from knee joints with a range in severity of osteoarthritis. The joints were examined radiographically, grossly, microradiographically, and histologically to characterize the severity of disease, and the results of three different methods of proteoglycan analysis (immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analysis) were compared. Subjectively, the degree of positive immunostaining for 7-D-4 was minimal in normal sites and increased as damage to articular cartilage increased. The scores for 7-D-4 immunostaining in the medial tibial plateau (the site most severely involved in this model) were correlated significantly with severity of damage to articular cartilage (p < 0.05, r2 = 0.50), thus supporting the subjective observations. The ratio of 7-D-4 to sulfated glycosaminoglycans in synovial fluid also was correlated with the score for 7-D-4 immunostaining in the medial tibial plateau (p < 0.05, r2 = 0.54) and with the score for 3-B-3 immunostaining in the medial femoral condyle (p < 0.05, r2 = 0.65). There were no significant correlations among scores for 3-B-3 immunostaining, severity scores, and the ratios of 3-B-3 to sulfated glycosaminoglycans in the synovial fluid. By Western blot analysis, both epitopes were sensitive markers of early cartilage damage in young adult monkeys but were less sensitive in older monkeys. This work provides evidence that measurement of the epitope recognized by 7-D-4 in synovial fluid or, by immunohistochemical or Western blot methods, in articular cartilage has potential use as a marker of severity of naturally occurring osteoarthritis.
Animals↗
Some objective measurements of frontal lobe deficits following traumatic brain injury.
The current study attempted to determine: 1) If frontal lobe TBI produces specific long-term cognitive deficits that are measurable on objective testing; and 2) Which tests are most appropriate for assessing frontal deficits. The study involved 41 patients: 10 sustaining TBI with frontal lesions on CT, 11 sustaining TBI without frontal lesions, and 20 controls. TBI subjects were included only if they were evaluated as outpatients to ensure that their cognitive deficits were stable, and not due to acute injury. The results suggest that: 1) Frontal lobe TBI produces a specific profile of cognitive deficits (characterized as inflexibility), with relative deficits on the Trail Making Test Part B and Rey AVLT that 6 (not trials 1-5), but generally intact performance on other cognitive measures: and 2) Tests useful in evaluating global cognitive dysfunction (i e, Rey AVLT) may need to be used differently for the specific evaluation of frontal lobe dysfunction.
Journal Article↗
Use of the Wechsler Memory Scale-Revised in traumatic brain injury.
The Wechsler Memory Scale-Revised (WMS-R) is a frequently used memory measure that has endured numerous criticisms, particularly related to the variability of results of factor analytic studies. The instrument relies on conglomerate Index scores to represent performance, in spite of tenuous empirical support. This study provides evidence that valuable information about memory abilities for individuals sustaining traumatic brain injury can be gained by investigating individual WMS-R subtest performance. The WMS-R was administered to a total of 54 subjects 36 individuals with moderate to severe TBI, and 18 normal controls. Results suggested that Index scores do not necessarily accurately represent performance on each of the individual Index subtests. Development of percentile scores for all subtests is strongly recommended, and implications for rehabilitation planning are discussed.
Journal Article↗
Identification and characterization of glycanated and non-glycanated forms of biglycan and decorin in the human intervertebral disc.
Immunological studies revealed the presence of several different forms of biglycan and decorin in human intervertebral-disc tissues (annulus fibrosus, nucleus pulposus and cartilage end-plate). In the young intervertebral disc, glycosaminoglycan-containing (glycanated) forms of both biglycan and decorin represented a greater proportion of the total proteoglycan population present in extracts of annulus fibrosus and cartilage end-plate compared with extracts of nucleus pulposus, in which they were barely detectable. In older discs the glycanated forms of biglycan and decorin represented only a small proportion of the total proteoglycan present. Immunochemical analyses with an antibody to chondroitin/dermatan sulphate isomers indicated differences in the glycosaminoglycans substituted on glycanated forms of small proteoglycans found in different disc tissues. Dermatan sulphate was the predominant glycosaminoglycan present on biglycan and decorin in annulus fibrosus extracts, whereas chondroitin 4-sulphate was present in both small proteoglycans isolated from cartilage end-plate. In addition, immunochemical analyses with antibodies against core protein epitopes identified two non-glycanated forms of both biglycan and decorin. These non-glycanated forms of the small proteoglycans were found in all three regions of the disc. The two nonglycanated forms of biglycan had estimated molecular masses of 37 and 41 kDa and those of decorin were 43 and 45 kDa, respectively. These non-glycanated forms of biglycan and decorin increased in proportion with aging. N-terminal sequence analysis indicated that the larger non-glycanated form of decorin was a degradation product of its glycanated precursor. However, no N-terminal sequence information was obtainable from the other non-glycanated form of decorin or the two non-glycanated forms of biglycan. These data are consistent with the hypothesis that some of the non-glycanated forms of decorin and biglycan are degradation products of native precursors. However, the possibility remains that several different post-translationally modified forms of decorin and biglycan are synthesized by intervertebral-disc tissues.
Adolescent↗
Immunohistochemical analysis of 3-B-(-) and 7-D-4 epitope expression in canine osteoarthritis.
OBJECTIVE: To examine the distribution of the 3-B-3(-) and 7-D-4 epitopes in proteoglycans from morphologically normal and osteoarthritic (OA) canine articular cartilage. METHODS: Cartilage samples from the femurs of stable and destabilized stifle joints of 9 dogs that had undergone transection of the cranial cruciate ligament were examined by immunohistochemistry. RESULTS: The 3-B-3(-) and 7-D-4 epitopes were expressed in the superficial zone of cartilage from the destabilized femorotibial joints in the early stages of developing OA. The staining patterns with these two antibodies differed, with 3-B-3(-) reactivity confined to the superficial and upper middle zones of the articular cartilage, and 7-D-4 reactivity more prominent in the matrix, extending into the deeper zones and increasing with progression of the lesion. Both epitopes were also expressed in the superficial and upper middle zones of areas peripheral to the lesions and were detectable before the loss of matrix and proteoglycans could be identified by histochemical staining with toluidine blue. CONCLUSION: In this study, the expression of atypical chondroitin sulfate proteoglycans was demonstrated in osteoarthritic canine cartilage, and the pattern of expression changed as the lesions progressed. The occurrence of 3-B-3(-) and 7-D-4 epitopes appears to be associated with changes in chondrocyte metabolism in the early stages of cartilage degeneration in experimental osteoarthritis.
Animals↗
The dynamic structure of the pericellular matrix on living cells.
Although up to several microns thick, the pericellular matrix is an elusive structure due to its invisibility with phase contrast or DIC microscopy. This matrix, which is readily visualized by the exclusion of large particles such as fixed red blood cells is important in embryonic development and in maintenance of cartilage. While it is known that the pericellular matrix which surrounds chondrocytes and a variety of other cells consists primarily of proteoglycans and hyaluronan with the latter binding to cell surface receptors, the macromolecular organization is still speculative. The macromolecular organization previously could not be determined because of the collapse of the cell coat with conventional fixation and dehydration techniques. Until now, there has been no way to study the dynamic arrangement of hyaluronan with its aggregated proteoglycans on living cells. In this study, the arrangement and mobility of hyaluronan-aggrecan complexes were directly observed in the pericellular matrix of living cells isolated from bovine articular cartilage. The complexes were labeled with 30- to 40-nm colloidal gold conjugated to 5-D-4, an antibody to keratan sulfate, and visualized with video-enhanced light microscopy. From our observations of the motion of pericellular matrix macromolecules, we report that the chondrocyte pericellular matrix is a dynamic structure consisting of individual tethered molecular complexes which project outward from the cell surface. These complexes undergo restricted rotation or wobbling. When the cells were cultured with ascorbic acid, which promotes production of matrix components, the size of the cell coat and the position of the gold probes relative to the plasma membrane were not changed. However, the rapidity and extent of the tethered motion were reduced. Treatment with Streptomyces hyaluronidase removed the molecules that displayed the tethered motion. Addition of hyaluronan and aggrecan to hyaluronidase-treated cells yielded the same labeling pattern and tethered motion observed with native cell coats. To determine if aggrecan was responsible for the extended configuration of the complexes, only hyaluronan was added to the hyaluronidase-treated cells. The position and mobility of the hyaluronan was detected using biotinylated hyaluronan binding region (b-HABR) and gold streptavidin. The gold-labeled b-HABR was found only near the cell surface. Based on these observations, the hyaluronan-aggrecan complexes composing the cell coat are proposed to be extended in a brush-like configuration in an analogous manner to that previously described for high density, grafted polymers in good solvents.
Animals↗
The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial.
Laboratory studies, and one previous uncontrolled trial, have suggested that retinoids may reverse bronchial atypia, a putatively premalignant condition. Sputum sampling is a simple, non-invasive method of assessing atypia. Smokers with at least a 15 pack-year history were screened for sputum atypia. One hundred and fifty subjects' were randomised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months. Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels. The outcomes assessed were, improvements in sputum atypia and toxicity. At baseline there was no significant difference between the two groups with respect to gender, smoking history or extent of atypia. Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months. Compliance as measured by pill counts and etretinate levels was high. Eighty-six per cent of subjects on etretinate took 90% or more of their prescribed medication and etretinate was detected in 245 of 264 samples. By contrast etretinate was detected in only six of 266 samples in the control group and probably did not represent true contamination. After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms. Toxicity was mild in both groups with considerable placebo effect noted. Etretinate, at the dose used in this study, had no impact on sputum atypia as detected by sputum sampling.
Administration, Oral↗
The fluid content of the human intervertebral disc. Comparison between fluid content and swelling pressure profiles of discs removed at surgery and those taken postmortem.
The fluid content of the disc, which governs its mechanical response and biological behavior, varies with external load. Because load on the disc changes after death, the fluid content and swelling pressure profiles of human discs taken at autopsy were measured, and compared with discs removed during surgical procedures. In general, discs taken at surgery had a lower fluid content in the nucleus and a higher fluid content in the outer anulus than discs removed at autopsy. In discs removed at surgery, the swelling pressure of the nucleus was higher than that of the anulus, whereas in autopsy discs the swelling pressure profile was flat. These changes are though to result from changes in load after death, and could influence the results of in vitro mechanical tests on the disc.
Biomechanical Phenomena↗
Proteoglycan secretory components of surface epithelial cells in postnatal ferret trachea.
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Animals↗
Anoxic encephalopathy: a case study of an eight-year-old male with no residual cognitive deficits.
Anoxia is generally associated with impaired learning, memory, attention, and planning. We present a case of near-drowning (5-15 minute anoxia) with subsequent 15 hour coma that is extremely unique because of (1) the absence of neuropsychological and neurological deficits 3 1/2 months post-injury, and (2) the availability of pre-injury intelligence testing for comparison. Findings are important as previous research has suggested residual deficits will be evident after much briefer coma. The present findings suggest anoxic encephalopathy does not automatically result in neurological or cognitive impairment.
Child↗
A meta-analysis of change in marital and employment status as predictors of alcohol consumption on a typical occasion.
Meta-analysis is used to combine results of primary data from 12 longitudinal studies to examine the consistency of results with respect to the role of changes on the individual level in marital status and employment status on changes in consumption of alcohol per typical occasion. The analyses control for the effects of Time 1 consumption per occasion and education. Not getting married and becoming unmarried are associated with increased consumption at follow-up and both variables are positively related to increased consumption among older men, but only becoming unmarried was related to increased consumption among older women. Becoming married is homogeneously and negatively associated with consumption at follow-up for younger and older persons of both sexes. Chronic unemployment is negatively related to consumption at follow-up among older males and younger females. Becoming unemployed between measurements is homogeneously and negatively related to consumption among older males and females, but positively related among younger males. Becoming employed is homogeneously and positively related to later consumption among all groups except young females.
Adolescent↗
A meta-analysis of depressive symptomatology and alcohol consumption over time.
Meta-analysis (eight general population longitudinal studies) describes the relationships (regressions) between quantity per occasion and depressive symptomatology over time. Quantity and depression are the strongest and most consistent predictors of final levels of themselves in all data sets. Age significantly and consistently predicts quantity for both sexes combined (the general pattern is replicated among males only). Depression significantly predicts quantity and quantity significantly predicts depression for females. Controlling for interval between measurements produces stronger prediction (more consistent over shorter intervals) for males. Depression only predicts quantity over longer intervals and quantity only predicts depression over shorter intervals for females. Explicit control for age found stronger relationships between initial and final measurement quantity, and depression for males. Quantity and depression significantly predict quantity and depression among young females. The relationship between quantity and depression among females illustrates the importance of controlling for age and sex. Methodological considerations are discussed.
Adult↗
Use of screening phase data to evaluate observer variation of sputum cytodiagnosis as an outcome measure in a chemoprevention trial.
Sputum samples obtained during the screening phase of a chemoprevention trial in heavy smokers were evaluated independently by trained cytotechnologists and classified for degree of cellular atypia according to the method of Saccommano et al. (G. Saccommano et al., Cancer (Phila.), 33: 256-270, 1974). The level of agreement within and between Observers A and B was calculated as the percentage of agreement and, in addition, a statistic was used (kappa) to correct for chance-expected agreement. Between observer agreement on 300 specimens from 130 subjects was 68% (204 of 300) (kappa = 0.58). Of the 96 disagreements, only 17 were of more than one category in the six-category classification. Within observer agreement for both Observers A and B was evaluated on a subset of 60 specimens from 49 subjects examined on two separate occasions by each observer. The percentage of within observer agreement was 80% for Observer A (kappa = 0.73) and 62% for Observer B (kappa = 0.49) (P less than 0.04). Altogether, 71% (25 of 35) of within observer discordant readings were confined to only one category. These data, obtained from the screening phase of the study, will allow us to refine the outcome measure for the trial without introducing bias that could result from knowledge of the actual study results. The failure of conventional cancer treatments to impact significantly on overall cancer mortality has led to an emphasis on prevention. If premalignant changes can be reliably detected at a time when the malignant process is reversible, then it may be feasible to intervene to prevent the occurrence of some cancers. The appropriate selection of subjects for such intervention trials and the subsequent demonstration of the efficacy of chemoprevention strategies are therefore crucial.
Etretinate↗