Search PubMed⌕ Search

Biomedical subjects

D J Williamson

Publications and source records attributed to D J Williamson.

At least 19 recordsLinked to original sources
PubMed1996

Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension. Their responses to inhaled NO predict their responses to other vasodilators, such as prostacyclin, and provide an estimate of the "fixed" component of their increased PVR. Some patients with limited cutaneous systemic sclerosis develop isolated pulmonary hypertension with a similar clinical course. Therefore, we have measured the acute hemodynamic response to inhaled NO in such patients. METHODS AND RESULTS: Seven patients were studied during inhalation of increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were collected on five patients. They demonstrated a selective, dose-dependent, and rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%). There was a nonsignificant increase in cardiac index but no change in mean arterial pressure or systemic vascular resistance. The mean right atrial pressure fell (27%), but there was no change in pulmonary artery occlusion pressure. Of the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease in total pulmonary resistance of at least 20%. CONCLUSIONS: Inhaled NO is an effective and selective pulmonary vasodilator in a significant number of patients with pulmonary hypertension associated with limited cutaneous systemic sclerosis. It may be useful in determining the potentially reversible contribution to the increased PVR and should be considered for patients with acute pulmonary vascular crisis.

Administration, Inhalation↗
PubMed1996

Ventral tegmental area injury and frontal lobe disorder.

A patient developed acute behavioral changes implicating frontal-executive dysfunction. His clinical signs suggested mesencephalic injury, and a cranial MRI scan showed an abnormality restricted to a small region of the ventral midbrain. We suggest that the patient's behavioral disorder originated from disruption of the ventral tegmental area or it projections, structures that influence frontal brain processes via the mesocortical dopamine tract.

Behavior↗
PubMed1996

Potential mechanisms by which nonsteroidal anti-inflammatory drugs elevate blood pressure: the role of endothelin-1.

To determine whether endothelin-1 (ET-1) contributes to hypertension associated with non-steroidal anti-inflammatory drug (NSAID) usage in healthy, elderly, normotensive individuals a randomised, double-blind, placebo-controlled, crossover trial of indomethacin was undertaken in 41 healthy, elderly individuals with stable normotension or controlled hypertension (blood pressure (BP) < or = 160/90 mm Hg). The main outcome measures were systolic and diastolic BP, heart rate, cardiac output, weight, creatinine clearance, plasma renin activity, aldosterone, endothelin-1 and arginine vasopressin concentrations and 24 h urinary endothelin-1 and 6 keto prostaglandin F1 alpha outputs. Analysis of covariance was used to evaluate the effect of indomethacin on BP and related parameters. Indomethacin treatment for 1 month increased systolic (+/- s.e.m.: 4.1 +/- 2.2 mm Hg; 95% confidence interval 0 to 8.3 mm Hg) and diastolic BP (2.7 +/- 1.1 mm Hg; 0.4 to 4.9 mm Hg) without altering cardiac output (P = 0.59), implying an increase in total peripheral resistance. Indomethacin treatment produced a small increase in weight (1.4 +/- 0.4 kg; 0.6 to 2.2 kg), a small reduction in renal function (creatinine clearance: 6.8 +/- 1.8 mis/min; 3.3 to 10.3 mis/min) but a significant (83%) increase in daily urinary endothelin-1 production (13.1 +/- 3.4 ng/ml; 6.4 to 19.8 ng/ml) without altering plasma ET-1 concentration, suggesting increased renal synthesis. In conclusion, renal paracrine effects of ET-1 may contribute to NSAID-induced blood pressure elevation in humans.

Aged↗
PubMed1995

Comparison of the effects of sumatriptan and the NK1 antagonist CP-99,994 on plasma extravasation in Dura mater and c-fos mRNA expression in trigeminal nucleus caudalis of rats.

Dural plasma extravasation produced by electrical stimulation of the trigeminal ganglion was measured in rats and the concomitant expression of c-fos mRNA produced in the trigeminal nucleus caudalis (NtV) was measured using in situ hybridization techniques. The non-peptide NK1 receptor selective antagonist CP-99,994 (1-3000 micrograms kg-1) and the 5HT1D receptor agonist sumatriptan (1-1000 micrograms kg-1) reduced dural plasma extravasation dose-dependently with ID50S of 52 micrograms kg-1 and 30 micrograms kg-1 respectively. CP-99,994 (1000 micrograms kg-1). a compound known to have good brain penetration, decreased c-fos mRNA expression in the NtV by 37 +/- 7% without disruption of the blood brain barrier (BBB). Sumatriptan (1000 micrograms kg-1), known to be poorly brain penetrant, had no significant effect on c-fos mRNA expression in the NtV unless the BBB was disrupted by infusion of a hyperosmolar mannitol solution after which sumatriptan decreased c-fos mRNA expression by 65 +/- 11%. The results suggest that brain penetrant NK1 receptor antagonists may have anti-migraine effects peripherally through blockade of dural extravasation and centrally by inhibition of nociceptive pathways. Furthermore the data indicates that the anti-migraine action of sumatriptan must be predominantly peripherally mediated, be it via inhibition of plasma extravasation or direct vasoconstriction, since it had little effect on the activation of neurones in the NtV unless the BBB was disrupted.

Animals↗
PubMed1995

Do the endocrine and subjective effects of d-fenfluramine predict response to selective serotonin reuptake inhibitors?

Thirty drug-free depressed patients underwent double-blind, placebo-controlled, neuroendocrine testing with the serotonin (5-HT) releasing agent d-fenfluramine prior to receiving treatment with a selective serotonin reuptake inhibitor (SSRI) for 8 weeks. Compared to placebo, d-fenfluramine significantly elevated plasma levels of prolactin and cortisol, increased subjective visual analogue ratings of "light headed" and decreased ratings of "desire to eat". Of the 30 patients studied, 17 responded to treatment but none of the pretreatment responses to d-fenfluramine distinguished patients who responded to SSRI treatment from those who did not. The results suggest that the clinical response to SSRI administration may be independent of pretreatment brain 5-HT function. Another possibility is that the neuroendocrine and subjective effects of d-fenfluramine are mediated by 5-HT mechanisms other than those involved in the antidepressant effect of SSRIs.

Adolescent↗
PubMed1995

Neglect of radial and vertical space: importance of the retinotopic reference frame.

Neglect from bilateral brain injury can disrupt responses along space defined by the vertical and radial axes. The spatial reference frames for vertical and radial neglect remain largely undefined, however. The viewer centred system, for example, consists of retinocentric and cephalocentric/corporacentric frames. In the present study, different viewer centred reference frames were dissociated in a patient with combined far radial superior vertical neglect through performance of radial line bisections above and below eye level. To separate reference frames for vertical space, bisections were performed while the patient was lying sideways. Results suggest that this patient's neglect respected a retinotopic viewer centred reference frame.

Adult↗
PubMed1995

Memory deficits in a demented patient with probable corticobasal degeneration.

Anterograde and retrograde amnesia in a patient with probable corticobasal degeneration (pCBD) and dementia were studied in a university medical center setting. The patient with pCBD and four comparison patients of comparable global mental status (Mini-Mental State Exam) who met NINCDS-ADRDA criteria for Alzheimer's disease (AD) were included. Standard neuropsychological tests of naming, intelligence, achievement, verbal fluency, anterograde and remote verbal and visuospatial memory, and motor skill learning were given. The pCBD patient exhibited a progressive asymmetric akinetic-rigid syndrome, which was unresponsive to Sinemet. His initially mild, intellectual deficits consisted of apraxia, slowed speech, and word-finding and memory difficulties. Over a 2-year period, a dementia syndrome developed, which involved more-serious deficits in praxis and naming, as well as impairments in spelling, calculation, verbal fluency, IQ, anterograde verbal and visuospatial memory, and motor skill learning. When tested by recall methods, the pCBD patient exhibited marked deficits on several tests of remote memory; however, on recognition testing, he performed normally on the Famous Faces Test and on a test of geographical knowledge, which measures remote visuospatial memory. By contrast, the four AD patients, who showed equivalent naming difficulties, less-severe fluency deficits, and normal motor skill learning, showed severe impairments in recalling and recognizing the names of famous people from photographs. A magnetic resonance imaging (MRI) scan of the pCBD patient showed marked frontal and parietal lobe atrophy and central atrophy, with ventriculomegaly that was greater on the left side of the brain. The temporal lobes were relatively spared, and the amygdalae, hippocampi, and temporal horns were of normal size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of valine on 5-HT-mediated prolactin release in healthy volunteers, and on mood in remitted depressed patients.

BACKGROUND: Animal experimental studies suggest that the amino acid valine may decrease brain serotonin (5-HT) function by inhibiting the transport of the 5-HT precursor, L-tryptophan, across the blood barrier. The aim of the present study was to assess whether valine could decrease brain 5-HT function in healthy subjects and provoke symptomatic relapse in recently remitted depressed patients taking antidepressant drug treatment. METHOD: We studied the effect of valine (30 g) on the prolactin (PRL) response to the 5-HT releasing agent, D-fenfluramine, in healthy male subjects and on the mood of 12 remitted depressed patients taking either selective serotonin re-uptake inhibitors (n = 10) or lithium and amitriptyline (n = 2). RESULTS: Valine significantly lowered the PRL response to D-fenfluramine in healthy subjects. In the remitted depressives, valine caused a mild but detectable lowering of mood on a number of measures but only one patient experienced a significant relapse in mood. CONCLUSIONS: Valine administration may decrease brain 5-HT neurotransmission in humans. This effect could explain the mild increase in depressive symptoms in patients taking 5-HT-potentiating drugs.

Adult↗
PubMed1994

The Nithsdale Schizophrenia Surveys. XII. 'Neurodevelopmental' Schizophrenia: a search for clinical correlates and putative aetiological factors.

BACKGROUND: The aim was to examine in a population of schizophrenic patients the clinical correlates of 'neurodevelopmental' schizophrenia and their relationship to putative aetiological factors. METHOD: Premorbid social adjustment, premorbid schizoid and schizotypal personality traits, and the obstetric history of 40 schizophrenic patients and their 102 sibs were assessed through interviews with their mothers. Patients' premorbid level of intelligence was assessed by the National Adult Reading Test and current symptoms by the Positive and Negative Syndrome Scale and the Subjective Deficit Syndrome Scale. RESULTS: Patients had more schizoid and schizotypal traits than their sibs. They showed a deterioration in social adjustment between childhood and adolescence; sibs' social adjustment improved. There were statistically significant associations between current negative schizophrenic symptoms, premorbid deterioration in social adjustment, and schizoid and schizotypal personality traits, and between an early age of onset of illness and the same premorbid assessments. There was no evidence that patients with a family history of severe mental illness leading to hospitalisation, or a history of definite obstetric complications, had poorer premorbid functioning or more severe current symptoms. CONCLUSIONS: We have confirmed clinical correlates of 'neurodevelopmental' schizophrenia but found no association between these and obstetric complications or a family history of severe mental disorder.

Adult↗
PubMed1994

The Nithsdale Schizophrenia Surveys. XIII. Parental rearing patterns, current symptomatology and relatives' expressed emotion.

BACKGROUND: A population of adult schizophrenic patients was assessed to discover how the patients viewed their childhood, whether their view differed from non-schizophrenic adults, and to determine any association between parental rearing practices as perceived by the patient, childhood personality as perceived by the mother, and current symptoms. Type and level of expressed emotion shown by parents towards patients was also examined. METHOD: Parental attitudes, as perceived by 50 schizophrenic patients, were assessed by the EMBU scale. Patients' premorbid personality and social adjustment were assessed through interviews with patients' mothers by the Scale for the Assessment of Premorbid Schizoid and Schizotypal Traits and the Premorbid Social Adjustment Scale. Current symptoms were assessed by the Positive and Negative Syndrome Scale and Subjective Deficit Syndrome Scale. RESULTS: Patients saw little difference between fathers' and mothers' attitudes. There was a positive correlation between parental rejection and overprotection, and a negative correlation between rejection and warmth. There were no significant correlations between parental rearing attitudes and patients' childhood personality; there was a significant correlation between parental attitudes and current symptoms. Rejection and overprotection were associated with more severe, warmth with less severe symptoms, especially so for positive schizophrenic symptoms and general psychopathology. Although there was no association between the general level of expressed emotion shown by the parent towards the adult patient, and patients' perceived parental rearing attitudes, parents with high expressed emotion on the basis of hostility had higher rejection scores on the parental rearing attitudes scale. CONCLUSIONS: Schizophrenic patients saw their parents as showing much less warmth, and the severity of currents symptoms was associated with perceived parental rearing attitudes. The hostility component of high expressed emotion may be a parental trait which exists before the illness begins.

Adult↗
PubMed1994

A technique to localize activation in the human brain with technetium-99m-HMPAO SPECT: a validation study using visual stimulation.

UNLABELLED: This study extends and validates a system for localizing brain activity changes based on fiducial markers, coregistration of SPECT and MRI structural images and atlas/MRI-assisted localization. METHODS: Ten normal subjects underwent 99mTc-HMPAO SPECT during a resting eyes-closed baseline measurement and during visual stimulation (8-Hz reversing checkerboard). SPECT scans were registered with MRI scans obtained from each individual using a fiducial-based system that minimized z-axis and rotational errors, and registration was further refined along the x- and y-axes by superimposing corresponding axial SPECT and MRI slices. Regions of interest (ROIs) were located on MRI slices with the aid of an atlas. Corresponding loci on SPECT slices were chosen and incrementally adjusted such that the center of a ROI was located precisely at the maximum of activity in the visual cortex or the cortical gray matter ribbon. RESULTS: Activity in the calcarine cortex increased by 44.39% during visual stimulation (p < 0.001). Adjustment of ROI location in accordance with local activity maxima yielded superior results to a method relying strictly on atlas/MRI localization. Premotor cortex activity declined by 16.91% on the right (p < 0.01) and 13.85% on the left (p > 0.05), whereas no changes occurred in the somatosensory cortex. CONCLUSION: Changes in visual cortical activity were most comparable to previous functional MRI studies but also congruent with PET and SPECT findings. Using the locus of peak activity to aid in defining cortical ROIs improves the signal-to-noise ratio by reducing noise related to inevitable minor registration errors.

Adolescent↗
PubMed1993

The non-peptide neurokinin1 receptor antagonist, RP 67580, blocks neurogenic plasma extravasation in the dura mater of rats.

A non-peptide neurokinin1 (NK1) receptor antagonist, RP 67580, that is selective for the rodent subtype of the NK1 receptor, dose-dependently reduced plasma extravasation in the dura mater produced by electrical stimulation of the trigeminal ganglion in rats, with an ID50 of 0.6 micrograms kg-1. Its enantiomer RP 68651 was some 400 fold less active. The results indicate that neurogenic plasma extravasation within the dura mater is NK1 receptor-mediated and suggest that NK1 receptor antagonists may have a role as antimigraine agents.

Animals↗
PubMed1993

Anabolic steroid use among students at a British college of technology.

To determine the rate of current or previous use of anabolic steroids by students at a UK college of technology, a questionnaire survey of 687 day students was conducted. The questionnaire began with a general section for all of the students, which ended with the question 'Have you ever used anabolic steroids?'. A further section specifically for anabolic steroid users examined patterns of use, and how certain circumstances might affect the individual's decision to use anabolic steroids. The response rate to the questionnaire was 92%. The overall rate of current or previous use of anabolic steroids was 2.8% (4.4% in males, 1.0% in females). Of these, 56% had first used anabolic steroids at age 15 or less. Anabolic steroid users were more likely to be male, under 17 years of age, and participating in bodybuilding, weight-lifting or rugby. The results of this survey, if confirmed in other groups of young people, would suggest that use of anabolic steroids may be widespread in the UK.

Adolescent↗
PubMed1993

Cholinergic treatment of an amnestic man with a basal forebrain lesion: theoretical implications.

Cholinergic deficient states, such as in Alzheimer's disease, are associated with amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease have had only equivocal results, but mechanisms other than cholinergic deficiency may contribute to the memory deficit. Normally the diagonal band of Broca provides much of the hippocampal cholinergic input. To learn if amnesia secondary to cholinergic deficiency can be ameliorated by cholinergic augmentation, we treated an amnestic man who had a lesion located primarily in the right diagonal band of Broca with physostigmine and lecithin. During the initial best-dose-finding phase, he demonstrated an inverted U-shaped curve for immediate recall of word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single photon emission tomography showed decreased blood flow in the medial temporal region ipsilateral to the lesion at baseline, with a reversal of the asymmetry on 3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on 3.5 mg of physostigmine, however, failed to demonstrate that cholinergic treatment improved memory.

Amnesia↗