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Biomedical subjects

J Whyte

Publications and source records attributed to J Whyte.

At least 55 records · Page 3Linked to original sources
PubMed1996

Improved arousal and initiation following tricyclic antidepressant use in severe brain injury.

Three patients with severe traumatic brain injury demonstrated significant improvement in arousal and initiation after administration of tricyclic antidepressants. The first patient showed improved motor and speech initiation in response to amitriptyline following several months of functional plateau. The second patient was minimally responsive 2 months after injury and demonstrated improved arousal following the use of desipramine. Both patients deteriorated when the medications were discontinued and improved again when they were restarted. These two cases provide strong evidence for a medication effect. The third patient began to verbalize following desipramine administration, despite being mute for more than a year after injury. Previous case reports describe cognitive-enhancing effects, such as improved arousal, attention, memory, and initiation, of dopaminergic agents, and in the case of tricyclic antidepressants, effects on agitation. The role of norepinephrine in promoting neurological recovery after brain lesions has been demonstrated in animals. The cases presented here provide some of the first data to show similar efficacy in humans and underscore the need for controlled trials to better determine which patients will benefit.

Activities of Daily Living↗
PubMed1996

Inattentive behavior after traumatic brain injury.

Clinicians and families report that traumatic brain injury results in a variety of attention deficits. Numerous laboratory studies have documented slowing of information processing, alteration in event-related potentials, or difficulty attending to specific relevant task dimensions in the presence of redundant information. However, little is known about how these information processing abnormalities relate to observable behaviors in daily living or work environments, which presumably form the basis for clinicians' and families' reports. We developed a quantitative assessment of behavioral inattentiveness in both quiet and distracting environments, and demonstrated excellent interrater reliability. Using this assessment, we have studied 20 patients with recent traumatic brain injury and 20 demographically comparable control subjects. We have confirmed marked differences in behavioral attentiveness between patients and controls in both distracting and nondistracting environments.

Activities of Daily Living↗
PubMed1996

Experimental vasectomy and testicular structure.

We have performed an experimental study on rats and dogs to evaluate the long term effects (from 1 to 12 months) of vasectomy on the structure of the testis. From four months after vasectomy onwards, the specimens showed very important changes in the seminiferous epithelium and Sertoli cells, with an obvious thickening of the basement membrane that supports the epithelium. The deterioration depended on the time passed and, over six months after vasectomy, the alterations were very clear and the seminiferous tubules became atrophic and shrunk, sometimes without any remains of seminiferous epithelium and with an important hypertrophy of the interlobular interstitial tissue, although we did not see an increase in the number of Leydig cells. Alterations due to vasectomy depend on the animal species, the peculiarities of techniques and, of course, the time passed after surgery.

Animals↗
PubMed1995

Segregation of autoantibodies with disease in monozygotic twin pairs discordant for systemic sclerosis. Three further cases.

OBJECTIVE: To study the serologic status of 3 previously unreported monozygotic twin pairs discordant for systemic sclerosis (SSc). METHODS: Autoantibodies were measured by indirect immunofluorescence, immunodiffusion, and immunoprecipitation of 35S-labeled cell lines. Major histocompatibility complex (MHC) class II allele typing and DNA fingerprinting were used to confirm monozygosity. RESULTS: Anti-PM-Scl, anti-threonyl transfer RNA synthetase, and anti-topoisomerase I antibodies, respectively, were found in each of the twins with SSc. None of the unaffected twin siblings had an identifiable autoantibody, although serum from 1 unaffected twin precipitated several unknown proteins. The MHC class II genotype in each twin was the genotype expected for the autoantibody that was present. CONCLUSION: Autoantibodies of certain defined specificities are intimately linked with the development of SSc, because they segregate with SSc in individuals who start life with identical germline genes.

Autoantibodies↗
PubMed1995

Sustained arousal and attention after traumatic brain injury.

Clinicians report that patients with traumatic brain injury (TBI) often have difficulty with tasks requiring sustained attention, and there are neuroanatomical and neurophysiological reasons to expect such deficits. Nevertheless, laboratory measures of sustained attention or vigilance in TBI have produced conflicting results. These inconsistencies may be due to patient heterogeneity as well as the fact that vigilance performance is dependent on highly specific features of the task design. We developed a visual vigilance task in which the influence of non-attentional factors was minimized and task difficulty for patients and controls made comparable. Performance was characterized with respect to vigilance level as well as vigilance decrement, using measures of perceptual discrimination, response bias, reaction time and reaction time variability. Twenty-six patients with recent TBI and 18 control subjects were tested on this task. A MANOVA of ranked scores revealed significantly different patient and control performance overall. Initial level of performance (vigilance level) was slower and more variable for patients than controls, and patients showed more conservative response biases. Deterioration over time (vigilance decrement) was steeper for patients than controls for reaction time, reaction time variability, and response bias. Deterioration in accuracy (D') did not differ significantly between patients and controls. Performance was not related to available measures of injury severity. Hypotheses relating arousal mechanisms to vigilance performance are discussed.

Adolescent↗
PubMed1995

Critical evaluation of clinical research.

This focused review contains a suggested core of material that will help residents or practicing physiatrists critically review research papers published in the medical literature. Before accepting the results of a clinical trial, physiatrists must critique the experimental methods and study design carefully to decide whether to include these new ideas into their clinical practice. Medical research relies on statistical methodology, and statistics pervade the medical literature. This article begins with an introduction to rudimentary statistics. Fortunately, most studies depend on a rather small body of statistical concepts. The elements of experimental design--clinical trials, randomization, single-subject design, meta-analysis, epidemiological studies--are presented in a concise review. Finally, the elements of statistics and experimental design are integrated into a step-by-step method strategy for reading the medical literature.

Epidemiologic Methods↗
PubMed1995

Assessment of vision and visual attention in minimally responsive brain injured patients.

Sensory, motor, and cognitive assessment is a critical priority in the care of minimally responsive brain-injured patients. However, their inconsistent pattern of responding may interfere with the use of traditional forms of assessment such as the mental status or neurological examinations. In this article we describe a quantitative method, based on single-subject experimental design, for evaluating vision and visual attention in this patient population. In a series of randomized trials, combinations of a blank card, a colorful photograph, and no stimulus are presented to either or both visual fields while horizontal eye movements are observed. The relationship between the side and nature of the visual stimulus and the frequency of eye movements is analyzed to determine visual function in one or both eyes. We report six cases of minimally responsive patients assessed with this method. In case A, we show evidence of functional vision in both visual fields. Case B also shows functional fields, but with a monocular visual deficit. Cases C and D show a homonymous hemianopsia which, in case D, is further complicated by a monocular visual deficit. Finally, cases E and F show patterns of left and right visual extinction. Thus, this objective and quantitative method leads to conclusions about patients' visual function that are not readily apparent by clinical observation and that allow appropriate modifications in further assessment or treatment.

Adolescent↗
PubMed1995

Frequency of autoantibodies to a major epitope on the carboxyl terminal fragment of CENP-B in patients with autoimmune disease.

The carboxyl-terminal fragment of CENP-B contains a major epitope for anti-centromere antibodies (ACA). We have developed an enzyme-linked immunoassay (ELISA) for measuring antibodies to the 147-carboxyl-terminal amino acids of CENP-B expressed as a beta-galactosidase fusion protein. The ELISA was 98% sensitive and 95% specific for detecting ACA in a population which included 46 patients with ACA detected by other means. Therefore, the CENP-B ELISA should prove a valuable tool in screening for ACA in populations at risk of developing systemic sclerosis, such as those with Raynaud's phenomenon. Levels of anti-CENP-B antibodies were not increased in unaffected relatives of probands with ACA.

Autoantibodies↗
PubMed1995

Detection of anti-topoisomerase I antibodies using a full length human topoisomerase I recombinant protein purified from a baculovirus expression system.

Topoisomerase I (topo I) is a major systemic sclerosis (SSc)-associated autoantigen. A cDNA construct encoding full length human topo I in a recombinant baculovirus transfer vector was used to infect insect cells in culture from which recombinant protein was purified. An ELISA using recombinant protein was evaluated in 340 sera including sera from 134 patients with SSc, of whom 33 had anti-topo I antibodies detected by immunodiffusion. A high yield of pure topo I of expected molecular mass and catalytic activity was obtained. The recombinant topo I ELISA was 92% sensitive and 98% specific in detecting anti-topo I antibodies which were present almost exclusively in patients with SSc. Therefore, the potential advantages of expressing human autoantigens in eukaryotic systems for diagnostic purposes were confirmed.

Animals↗
PubMed1995

Characterisation of anticytoplasmic antibodies and their clinical associations.

OBJECTIVES: To characterise the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) of human epithelial (HEp-2) cells and the antigens recognised using additional serological techniques. To define the disease associations of anticytoplasmic antibodies. METHODS: Sera from 1173 patients were screened for cytoplasmic IF staining on HEp-2 cells and the patterns characterised. The presence of antimitochondrial antibodies (AMA) was evaluated by a sensitive anti-pyruvate dehydrogenase complex enzyme linked immunosorbent assay (ELISA) (IgG) and by immunoblotting. Detection of antibodies to extractable nuclear antigens (ENA) was performed by double immunodiffusion and the presence of anti-ribosomal P antibodies was determined by immunoblotting. RESULTS: Cytoplasmic IF staining was demonstrated in 75 sera (6.4%). Six different patterns were recognised: coarse granular filamentous speckles (AMA, n = 9); condensed large speckles (anti-golgi apparatus antibodies, n = 3); cytoskeletal (n = 9); centriolar (n = 4); diffuse coarse speckles (n = 33); and fine speckles (n = 17). Of the nine sera with an AMA pattern, the presence of these antibodies was confirmed in seven by the ELISA (n = 6) and on immunoblotting (n = 7). One of the seven patients had primary biliary cirrhosis, and two had scleroderma. Two patients with anti-golgi antibodies had rheumatoid arthritis and two with anticentriolar antibodies had scleroderma. Of 33 sera that had cytoplasmic staining and were ANA negative, three were positive for anti-Ro and two were positive for anti-Jo-1 antibodies. CONCLUSIONS: In general, defined cytoplasmic IF patterns have no specific disease associations. However, the finding of cytoplasmic fluorescence should not be ignored, as it may indicate the presence of antibodies to ENA in the absence of nuclear staining.

Antibodies, Antinuclear↗
PubMed1994

Anti-topoisomerase I antibodies in silica-associated systemic sclerosis. A model for autoimmunity.

OBJECTIVE: To determine the frequency and type of autoantibodies present in patients with systemic sclerosis (SSc) associated with an established environmental toxin. METHODS: Clinical data and sera were available from 14 men with silica-associated SSc who had developed SSc after at least 2 years of exposure to silica at work. Controls included 27 men with silicosis without SSc. Autoantibodies were measured by immunodiffusion, immunoblotting, and functional inhibition of topoisomerase I (topo I). RESULTS: Nine of the 14 patients with silica-associated SSc had anti-topo I antibodies. All anti-topo I antibodies in the patients with silica-associated SSc and in 14 anti-topo I-positive patients with idiopathic SSc were directed at an active site of topo I, or at least sterically inhibited its function. One patient with silica-associated SSc had anticentromere antibodies. Unexpectedly, 2 patients with silicosis who had no symptoms of a connective tissue disease had autoantibodies to Ro/SS-A and La/SS-B autoantigens. CONCLUSION: Anti-topo I antibodies are the predominant autoantibodies present in silica-associated SSc. The generation of anti-topo I antibodies in genetically susceptible individuals may depend partly on the patient's sex and on the site of organ involvement, and may be triggered by silica particles acting as an immune adjuvant.

Aged↗
PubMed1994

The association of primary biliary cirrhosis and systemic sclerosis is not accounted for by cross reactivity between mitochondrial and centromere antigens.

A proportion of patients with primary biliary cirrhosis (PBC) develop the CREST variant of systemic sclerosis (SSc) and in these individuals antimitochondrial antibodies (AMA) and anticentromere antibodies (ACA) coexist. Immunological cross-reactivity between mitochondrial and centromere-associated antigens might account for the clinical and serological overlap between these conditions. Therefore, antibodies were affinity purified from the 70 kD polypeptide corresponding to the E2 component of the pyruvate dehydrogenase complex (PDHC) and from CENP-C, a 140 kD centromere-associated protein, to examine this possibility. Although the purified antibodies reacted with their corresponding antigens, no evidence of shared determinants between the 70 kD protein and CENP-C could be detected whether the antibodies were prepared from monospecific sera or from sera containing both AMA and ACA. Therefore, AMA and ACA present discrete autoantibody populations which may coexist in the same patient and may influence the clinical picture but have both structural and immunologically independent antigenic targets.

Aged↗
PubMed1994

HLA-DQB1 associations with anti-topoisomerase-1 antibodies in patients with systemic sclerosis and their first degree relatives. United Kingdom Systemic Sclerosis Study Group.

The frequency and functional properties of anti-topoisomerase-1 antibodies (ATA) have been studied in 58 systemic sclerosis (SSc) probands, 218 first degree relatives and 22 spouses. The dependence of ATA on the presence of certain HLA-DRB1 and HLA-DQB1 alleles was examined. ATA were detected by immunodiffusion, by absorption or inhibition of topoisomerase-1 enzymic activity, by immunoblotting of a K562 cell extract and by immunoprecipitation of 35S radiolabelled cell lines. HLA class II typing for HLA-DRB1 and HLA-DQB1 was performed by oligonucleotide typing in 49 families. Six probands and two relatives had ATA. The relatives with ATA had SSc. All eight individuals with ATA directly inhibited topoisomerase-1 function. Four of the eight had limited skin disease and four had diffuse skin involvement. The seven who were genotyped had at least one HLA-DQB1 allele encoding for tyrosine at position 30 of the first domain. Therefore, ATA are not widely dispersed within families, but rather are only present in those with SSc, and certain genetic requirements appear necessary for their generation.

Alleles↗
PubMed1994

Familial scleroderma--evidence for environmental versus genetic trigger.

Families with more than one case of scleroderma are unusual. Four families each with two members (in one case monozygotic twins) with scleroderma (systemic sclerosis, SSc) were identified. Clinical, immunogenetic and autoantibody studies were carried out. Multicase SSc families cited in the literature were reviewed. Each family pair shared cutaneous subset of disease severity, and SSc-associated autoantibody. HLA typing showed two pairs shared an HLA-DR allele associated with scleroderma (DR3 or DR5), while one also had alleles reported in association with their SSc-specific autoantibody. Review of dates and ages of onset suggested that the timing of onset of scleroderma is more likely to have an environmental trigger than to be encoded genetically.

Adult↗
PubMed1994

Anti-centromere antibodies (ACA) in systemic sclerosis patients and their relatives: a serological and HLA study.

Autoantibody reactivity to centromere proteins CENP-A, CENP-B and CENP-C was examined in 58 patients with systemic sclerosis (SSc), 218 first degree relatives and 22 spouses. HLA class II typing for HLA-DRB1 and HLA-DQA1 was performed by restriction fragment length polymorphism (RFLP) analysis in 50 families, and HLA-DRB1, HLA-DQA1 and HLA-DQB1 typing was performed by olignucleotide typing in 44 families. Eleven probands and two relatives had ACA. The two relatives with ACA also had SSc. One relative was an identical twin sister of a proband with ACA and the other relative was a sister of a proband with ACA. All ACA-positive probands and relatives were female, and all recognized CENP-A, CENP-B and CENP-C. The presence of at least one HLA-DQB1 allele not coding for leucine at position 26 of the first domain appeared necessary, although not sufficient for the generation of ACA. Therefore within SSc families ACA is strongly associated with female gender and disease phenotype, and is at least in part genetically determined.

Alleles↗
PubMed1994

Frequency and clinical associations of anti-chromo antibodies in connective tissue disease.

OBJECTIVES: To assess the frequency and clinical associations of anti-chromo antibodies in connective tissue disease and to study their relationship to anti-centromere autoreactivity. METHODS: Anti-chromo and anti-centromere antibodies (ACA) were measured by immunoblotting in 50 patients with systemic sclerosis (SSc) and 58 connective tissue disease controls. Common epitopes on centromere and chromo antigens were sought using affinity-purified antibodies from immunoblots. RESULTS: Anti-chromo antibodies were detected in three of 32 sera with ACA and no controls. The three patients with anti-chromo antibodies had limited cutaneous SSc, and two had erosive arthritis. No cross-reactivity between chromo or centromere-related proteins was demonstrated. CONCLUSIONS: Anti-chromo antibodies form a rare autoantibody specificity that may identify an overlap group of patients with SSc and arthritis. Chromo and centromere antigens are associated but immunologically distinct autoimmune targets. Whether they localise to the same chromosomal site remains unknown.

Antibodies, Antinuclear↗