Search PubMed⌕ Search

Biomedical subjects

A Kirk

Publications and source records attributed to A Kirk.

At least 37 records · Page 2Linked to original sources
PubMed1999

Line bisection performance of normal adults: two subgroups with opposite biases.

BACKGROUND: Unilateral neglect patients may have either attentional or intentional neglect or both. Determining whether normal individuals are influenced by attentional or intentional biases will lead to a better understanding of the two types of neglect. Normal individuals may not be a homogeneous group. OBJECTIVE: To determine whether normal individuals show attentional/sensory or intentional/premotor biases when completing line bisections. METHODS: Thirty-two normal right-handed individuals participated. On each trial, participants were asked to move a cursor using a computer mouse to the midpoint of a line presented on a computer screen. The line could appear centered on or toward either side of the screen. Participants completed the task under two conditions: either the cursor moved in the same direction as the mouse (direct condition) or the cursor moved in the opposite direction as the mouse (indirect condition). RESULTS: Twenty-five participants showed an attentional bias, 3 showed an intentional bias, and 4 showed no bias. Of those with an attentional bias, 13 were biased to the left, and 12 were biased to the right. Those with a right-attentional bias made larger errors when the line was presented to the left, whereas those with a left-attentional bias made larger errors when the line was presented to the right. CONCLUSIONS: Our finding that the two attentional-biased groups produced the opposite pattern of results across the three line positions suggests the processes underlying performance in the two groups may in fact differ. Further study of these two groups may lead to a better understanding of unilateral neglect.

Adult↗
PubMed1999

5-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor.

1. The 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in isolated human small muscular pulmonary arteries (SMPAs) were determined using techniques of wire myography and reverse transcription-polymerase chain reaction (RT - PCR). 2. The agonists 5-HT, 5-carboxamidotryptamine (5-CT, unselective for 5-HT1 receptors) and sumatriptan (selective for 5-HT1B/D receptors) all caused contraction and were equipotent (pEC50s: 7.0+/-0.2, 7.1+/-0.3 and 6.7+/-0.1, respectively) suggesting the presence of a 5-HT1 receptor. 3. Ketanserin (5-HT2A-selective antagonist, 0.1 microM) inhibited 5-HT-induced contractions only at non-physiological/pathological concentrations of 5-HT (>0.1 microM) whilst GR55562 (5-HT1B/1D-selective antagonist, 1 microM) inhibited 5-HT-induced contractions at all concentrations of 5-HT (estimated pKB=7.7+/-0.2). SB-224289 (5-HT1B-selective antagonist, 0.2 microM) inhibited sumatriptan-induced contractions (estimated pKB=8.4+/-0.1) whilst these were unaffected by the 5-HT1D-selective antagonist BRL15572 (0.5 microM) suggesting that the 5-HT1B receptor mediates vasoconstriction in this vessel. 4. RT - PCR confirmed the presence of substantial amounts of mRNA for the 5-HT2A and 5-HT1B receptor subtypes in these arteries whilst only trace amounts of 5-HT1D receptor message were evident. 5. These findings suggest that a heterogeneous population of 5-HT2A and 5-HT1B receptors co-exist in human small muscular pulmonary arteries but that the 5-HT1B receptor mediates 5-HT-induced vasoconstriction at physiological and pathophysiological concentrations of 5-HT. These results have important implications for the treatment of pulmonary hypertension in which the 5-HT1B receptor may provide a novel and potentially important therapeutic target.

Base Sequence↗
PubMed1999

Clonally unrelated BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronic myeloid leukemia.

We report a patient with Philadelphia (Ph)-positive, BCR-ABL rearrangement positive, chronic myeloid leukemia (CML) with a prolonged chronic phase of 24 years who was first prescribed alpha-2 interferon 22 years after initial diagnosis. This therapy was tolerated poorly on account of thrombocytopenia, but an eventual major cytogenetic response was followed soon afterwards by transformation to terminal acute myeloid leukemia (AML). Cytogenetic studies indicated that the transformed myeloblasts were karyotypically normal and Ph negative. Although polymerase chain reaction (PCR) analysis of total leukemic mRNA remained BCR-ABL positive, other molecular studies, including Southern blotting and fluorescent in situ hybridization (FISH) analyses, showed that myeloblasts were BCR-ABL rearrangement negative. PCR-based clonality studies using an X-chromosome-linked restriction fragment polymorphism within the phosphoglycerate kinase gene (PGK1) further showed that the Ph-negative blast cells had a different clonal origin from the Ph-positive clone of chronic phase. We suggest that cases of underlying Ph-negative leukemic transformation in Ph-positive CML warrant further study and should be considered for trial of intensive remission induction therapy as appropriate for acute leukemia.

Acute Disease↗
PubMed1998

Analysis of primate renal allografts after T-cell depletion with anti-CD3-CRM9.

BACKGROUND: FN18-CRM9 is a CD3-specific immunotoxin that is capable of depleting CD3+ T cells. Pretreatment of rhesus monkeys with this agent before transplantation can induce donor-specific tolerance and "split tolerance" to renal allografts. METHODS: Heterotopic renal transplants were performed on monkeys that received posttransplant FN18-CRM9. Histological and immunohistological staining, as well as analysis of the intragraft cytokine profile by reverse transcriptase polymerase chain reaction, was performed on percutaneous allograft biopsies. RESULTS: Experimental monkeys had significant prolongation of allograft survival. Although an interstitial, mononuclear cell infiltrate was seen in all of the renal transplants, there was minimal evidence of acute cellular rejection. Histological evidence of alloantibody-mediated damage was detected 3 to 5 months after transplantation in the monkeys treated with FN18-CRM9. Immunohistology demonstrated the reappearance of CD3+ and CD4+ T cells, as well as CD20+ B cells, in the grafts. Cytokine analysis demonstrated expression of interferon-gamma. An intact anti-donor IgG response was seen. CONCLUSION: Treatment of monkeys with FN18-CRM9 immediately after transplantation significantly prolongs renal allograft survival. Allograft biopsies demonstrate a lack of acute cellular rejection; however, alloantibody-mediated graft damage and rejection occur, with an intact anti-donor IgG response. The intragraft expression of the interferon-gamma may reflect this ongoing humoral rejection. These data suggest that even a brief period of T-cell allosensitization may lead to humorally mediated allograft damage. Efforts to achieve tolerance with posttransplant FN18-CRM9 will require modification of the protocol to deplete T cells before allosensitization exposure or to supplement the posttransplant immunomodification strategy.

Animals↗
PubMed1998

Drawing with the non-dominant hand: implications for the study of construction.

BACKGROUND: Constructional impairment following left vs. right hemisphere damage has been extensively studied drawing tasks. A confounding factor in these studies is that right-handed patients with left hemisphere damage (LHD) are often forced by weakness to use their non-dominant (left) hand or hemiparetic dominant hand. Qualitative differences in the drawing characteristics of left and right hand drawings by normal subjects have not previously been characterized. The present study was undertaken to determine the qualitative differences between left and right hand drawings of normal subjects. METHODS: Thirty right-handed, elderly subjects without a history of neurological disease were asked to draw, from memory, seven objects using the right and left hand. Half of the subjects were randomly assigned to draw with the left hand first, and half the right hand first. Right and left hand drawings were compared using a standardized scoring system utilized in several previous studies of drawing in focal and diffuse neurological disease. Each drawing was scored on eighteen criteria. Right and left hand drawing scores were then compared using the t-test for paired samples or the Wilcoxon matched-pairs test. RESULTS: Drawings made using the left hand were found to be significantly simpler, more tremulous and of poorer overall quality than drawings made by the same subjects using the right hand. CONCLUSIONS: The deficits found in left versus right hand drawings of normals are similar to those found in patients with LHD, suggesting that much of the drawing impairment seen following LDH is due to an elementary motor disturbance related to use of the non-dominant hand.

Aged↗
PubMed1998

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.

Adult↗
PubMed1997

The complex interaction of normal biases in line bisection.

To better understand neglect it is necessary to understand the inherent biases of normal subjects. We attempted to determine whether the biases present in normal subjects' line bisection are based on visual and representational biases or whether misbisection is simply due to perceptual/illusionary biases toward the narrower end of the stimulus. Normal subjects' bisected lines presented in four orientations: horizontal, vertical, and radial (both above and below eye level). Arrowheads were chosen as the stimulus placed at each end of the line. Misbisection toward the narrow end of the arrow would support the hypothesis that bisection bias is based on illusionary factors. However, in all four orientations subjects erred toward the wider end of the arrow. This suggests that the visual and representational biases that underlie normal subjects' upward bias on bisecting vertical and radial lines cannot be explained solely on the basis of a perceptual/illusionary bias.

Adult↗
PubMed1996

A normal bias toward a pictorially defined top in line bisection.

BACKGROUND: We set out to determine whether separable visual and representational components underlie normal subjects' upward and distal biases in bisecting vertical and radial lines under visual guidance. METHODS: Thirty-four normal subjects were asked to bisect lines oriented horizontally, vertically, and radially. Human silhouette figures were placed at either end of each line. These figures were presented upright or upside down in order to pictorially define a "top" to each line independent of the actual top of the visual field. RESULTS: Although subjects erred toward the top of the visual field, they also demonstrated a significant bias toward the heads of the figures for lines in all spatial orientations. CONCLUSIONS: This result supports the existence of two biases: one toward the upper visual field, and another toward an internally represented "top" as suggested pictorially. These findings provide further support for the hypothesis that normal subjects' upward and distal biases on bisection of vertical and radial lines under visual guidance have both representational and visual-based components.

Adult↗
PubMed1994

Unilateral Creutzfeldt-Jakob disease presenting as rapidly progressive aphasia.

A 64-year-old man presented with a three day history of progressive Broca's aphasia, followed within 3 weeks by exclusively right-sided myoclonus, rigidity, and dystonia. Within 4 weeks he was globally aphasic. He died within 7 weeks of onset. In the final week, rigidity and myoclonus became bilateral. CT and MRI were normal. SPECT showed diminished perfusion of the left hemisphere. EEG showed periodic discharges on the left. At autopsy, there were marked cortical spongiform change, neuronal loss, and gliosis throughout the left hemisphere and in the right occipital cortex. Elsewhere in the right hemisphere, spongiform change was non-existent to minimal. There was moderate spongiform change in the molecular layer of the cerebellar cortex, much more marked on the left. Clinical and pathological unilateral cerebral predominance extended to the ipsilateral cerebellum. Creutzfeldt-Jakob disease is an important consideration in patients with rapidly progressive unilateral cerebral signs associated with a movement disorder.

Aphasia, Broca↗
PubMed1994

A representational vertical bias.

We attempted to determine whether separable components underlie normal subjects' upward bias in bisecting vertical and radial lines under visual guidance. Twelve normal subjects indicated the midpoint of visually presented lines oriented vertically, radially, and horizontally. We placed directional labels ("TOP" and "BOTTOM") at either end of each line. Subjects showed significant bias toward the label TOP in horizontal, vertical, and "radial-down" (below eye level) conditions but not in the "radial-up" (above eye level) position. In the horizontal condition, the misbisections actually changed direction depending on whether TOP was to the left or right of midpoint. There were two biases: one toward an internally represented "top" (as suggested by the verbal labels) and another toward the upper visual field. The latter was stronger when the two were opposed. These findings suggest that normal subjects' upward bias on bisection of vertical and radial lines under visual guidance has both representational- and visual field-based components.

Adult↗
PubMed1993

Subcortical contributions to drawing.

Constructional impairment is often considered a sign of cortical damage. However, aphasia, agraphia, and apraxia, disorders traditionally deemed cortical, have been well described following subcortical lesions, suggesting an important role for subcortical structures in cognition. Drawing impairment following subcortical lesions has not been systematically explored or compared with that following cortical damage. We examined relative incidence and severity of drawing impairment after cortical and subcortical strokes and whether there were qualitative differences between these two groups' drawings. Drawings by 125 patients with single hemispheric strokes of similar volume (42 left cortical, 36 left subcortical, 20 right cortical, 27 right subcortical) were compared using a standardized scoring system. Although previously noted right/left differences were confirmed, "subcortical drawings" did not differ from "cortical drawings" on any measures, including overall impairment. Compared with cortical patients, drawing impairment in those with subcortical lesions (especially left) was more strongly associated with impairment of other cognitive abilities. Thus, although a subcortical lesion does not cause more severe drawing impairment, subcortical lesions affecting drawing lead to more widespread cognitive dysfunction than do similarly sized cortical lesions. Drawing impairment often follows subcortical strokes and is by no means an indicator of cortical lesion localization.

Aged↗
PubMed1993

Cardioembolic caudate infarction as a cause of hemichorea in lupus anticoagulant syndrome.

An association exists between antiphospholipid antibodies and chorea. As these antibodies are associated with thrombosis, it has been suggested that cerebral infarction might cause chorea. However, CT and MRI typically do not demonstrate focal basal ganglionic lesions in such patients and an autoimmune mechanism for chorea has also been proposed. We report a young woman with left hemichorea and dyspnea. She was found to have lupus anticoagulant, large aortic and tricuspid vegetations, and pulmonary emboli. CT and MRI showed a small lesion in the head of the right caudate. In the presence of a definite cardiac source for emboli (valvular vegetations) with embolic activity (pulmonary emboli), it is likely that this patient's hemichorea was caused by cardioembolic caudate infarction.

Adult↗
PubMed1991

On drawing impairment in Alzheimer's disease.

Spontaneous drawings of 38 patients, diagnosed by the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria as "probable Alzheimer's disease," and of 39 normal control subjects were analyzed by two independent observers using a standardized scoring system. Drawings of patients with Alzheimer's disease displayed fewer angles, impaired perspective and spatial relations, simplification, and overall impairment compared with those of the control subjects. This represents a combination of the deficits seen following right- and left-hemisphere lesions. Neglect, tremor, and perseveration were not prominent. Drawing impairment was relatively independent of language or memory impairment, but drawing performance was related to perceptual and executive dysfunction in the visuospatial domain. Deterioration was followed up for up to 3 years.

Aged↗