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Biomedical subjects

A Gillies

Publications and source records attributed to A Gillies.

At least 19 recordsLinked to original sources
PubMed2004

Models of the subthalamic nucleus. The importance of intranuclear connectivity.

A coherent set of models is presented that provide novel and testable predictions about the functional role of the subthalamic nucleus (STN) in the basal ganglia. The STN is emerging as an important target for novel therapeutic strategies for the alleviation of Parkinsonian type symptoms [Lancet 345 (1995) 91; Science 249 (1990) 1436]. Computational and mathematical models based on the properties of the STN and its interactions are reviewed. These models focus on core anatomical and physiological data that span many levels. By assessing models of anatomy, dynamic network models, and a detailed model of a recent pharmacological experiment, we can expose the primary modes of STN function and highlight their underlying properties. We show that the presence of functional interactions between STN projection neurons is critical in defining its behaviour and how it interacts with other basal ganglia nuclei. Pulses or switch-like activity patterns emerge in the models as a consequence of these local interactions. Furthermore, the models demonstrate that this behaviour can break down under abnormal conditions resulting in low frequency bursting oscillations. Such oscillations may play a role in symptoms of Parkinson's disease.

Action Potentials↗
PubMed2003

Arm position and blood pressure: a risk factor for hypertension?

The objective of this study was to re-evaluate the effect of arm position on blood pressure (BP) measurement with auscultatory and oscillometric methods including ambulatory blood pressure monitoring (ABPM). The setting was the hospital outpatient department and the subjects chosen were normotensive and hypertensive. The effect of lowering the arm from heart level on indirect systolic BP (SBP) and diastolic BP (DBP) measurement as well as the importance of supporting the horizontal arm were measured. In the sitting position, lowering the supported horizontal arm to the dependent position increased BP measured by a mercury device from 103+/-10/60+/-7 to 111+/-14/67+/-10 mmHg in normotensive subjects, a mean increase of 8/7 mmHg (P<0.01). In hypertensive subjects, a similar manoeuvre increased BP from 143+/-21/78+/-17 to 166+/-29/88+/-20 mmHg, an increase of 23/10 mmHg (P<0.01). Combined results from normotensive and hypertensive subjects demonstrate a direct and proportional association between BP (SBP and DBP) and the increase produced by arm dependency. Similar changes and associations were noted with oscillometric devices in the clinic situation. However, supporting the horizontal arm did not alter BP. Of particular interest, analysis of 13 hypertensive subjects who underwent ABPM on two occasions, once with the arm in the 'usual' position and once with the arm held horizontally for BP measurement during waking hours, demonstrated changes comparable to the other devices. The mean 12-hour BP was 154+/-19/82+/-10 mmHg during the former period and significantly decreased to 141+/-18/74+/-9 mmHg during the latter period (P<0.01). Regression analysis of the change in SBP and DBP with arm position change again demonstrated a close correlation (r(2)=0.8113 and 0.7273; P<0.001) with the artefact being larger with higher systolic and diastolic pressures. In conclusion, arm movements lead to significant artefacts in BP measurement, which are greater, the higher the systolic or diastolic pressure. These systematic errors occur when using both auscultatory and oscillometric (clinic and ABPM) devices and might lead to an erroneous diagnosis of hypertension and unnecessary medication, particularly in individuals with high normal BP levels. Since clinical interpretations of heart level vary, the horizontal arm position should be the unambiguous standard for all sitting and standing BP auscultatory and oscillometric measurements.

Adolescent↗
PubMed2000

Computational models of the basal ganglia.

Computer simulation studies and mathematical analysis of models of the basal ganglia are being used increasingly to explore theories of basal ganglia function. We review the implications of these new models for a general understanding of basal ganglia function in normal as well as in diseased brains. The focus is on their functional similarities rather than on the details of mathematical methodologies and simulation techniques. Most of the models suggest a vital role for the basal ganglia in learning. Although this interest in learning is partly driven by experimental results associating the acute firing of dopamine cells with reward prediction in monkeys, some of the models have preceded the electrophysiological results. Another common theme of the models is selection. In this case, the striatum is seen as detecting and selecting cortical contexts for access to basal ganglia output. Although the behavioral consequences of this selection are hard to define, the models provide frameworks within which to explore these ideas empirically. This provides a means of refining our understanding of basal ganglia function and to consider dysfunction within the new logical frameworks.

Animals↗
PubMed2000

Assessing and improving the quality of information for health evaluation and promotion.

Studies by the author based upon a sample of over 1.1 million patients in the North West of England have shown that the introduction of computers cannot be demonstrated to produce significant improvements in health promotion activity. Other studies have revealed error rates in healthcare information systems in excess of 50%. This paper considers the reasons for these findings and demonstrate that there is a level of maturity of information management required before information systems can make a significant contribution to health promotion and evaluation. With the advent of locality commissioning and a re-affirmation of the emphasis upon health promotion activity set out in Health of the Nation and Our Healthier Nation [8], the role of information management has become even more significant. The paper presents a maturity model developed by the author, known as General Practice Information Maturity Model (GPIMM) that provides a strategic framework to improve the use of information by practices and to improve practice to enable viable sharing of accurate information. The paper will show the model can be used as a basis for the development of training and information strategies. The model identifies computerised practices as being in one of five stages of maturity: (1) Computerised, (2) Computerised PHC Team, (3) Coded, (4) Bespoke, (5) Paperless. The model specifically leads practices to a point in their development where they are able to carry out health evaluation, promotion and audit activities as a routine activity. Once these activities form part of practice activity they are then extended to encompass a group of practices such as a Primary Care Group. Finally, a case study is presented to show how the model was used to enable two very different but geographically neighbouring practices to work together towards the establishment of a common dataset. This dataset will be used to enable health promotion and evaluation activity to be provided for a total population of over 20,000 patients.

England↗
PubMed1998

Effect of diuretics on sodium and chloride permeability in the rat papillary collecting duct.

While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 micrometer/s), although both were relatively impermeable when compared to water. Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04 +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10(-4)) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.

Amiloride↗
PubMed1997

Pro-haemorrhagic effects of calcium antagonists: a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects.

It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatous effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointestinal bleeding. We identified 43 subjects from general practice with uncomplicated mild to moderate hypertension to compare the effects of the calcium antagonist isradipine with that of the beta-blocker atenolol on platelet function, plasma beta-thromboglobulin levels, fibrinolysis, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenolol produced comparable and clinically significant falls in blood pressure (167 +/- 2/102 +/- 1 to 153 +/- 3/91 +/- 2 mm Hg, and 165 +/- 2/101 +/- 1 to 156 +/- 4/91 +/- 2 mm Hg, respectively), neither drug produced a detectable effect on ex vivo platelet aggregation, platelet retention, or thromboxane generation with adrenaline, collagen, adenosine-di-phosphate, or platelet activating factor. However a decrease in plasma beta-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine but not the atenolol group. A 39% reduction with isradipine compared with 34% following atenolol treatment. Euglobulin clot lysis time was not altered by either drug. Serum cholesterol concentrations were also unaltered by drug treatment. Therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function after several weeks of treatment. However, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.

Adrenergic beta-Antagonists↗
PubMed1997

Numerical chromosomal aberrations in Hodgkin's disease detected by in situ hybridisation on routine paraffin sections.

AIMS: To visualise directly numerical chromosomal aberrations and polyploidy in both Hodgkin and Reed Sternberg (HRS) cells and background cells from cases of Hodgkin's disease using in situ hybridisation. METHODS: Non-isotopic DNA in situ hybridisation was applied to interphase cell nuclei of Hodgkin's disease within routine paraffin embedded tissue sections. Two a satellite DNA probes, specific for chromosomes 3 and 12, were used to evaluate the feasibility of this approach. Double labelling with immunocytochemical detection of the CD30 antigen was used to identify HRS cells. Cytogenetic normal diploid and triploid placental tissue served as controls. RESULTS: The eight cases of Hodgkin's disease investigated displayed frequent polysomy, while the majority of background cells showed disomy signals. CONCLUSIONS: Numerical chromosomal aberrations were detected in HRS cells from eight cases of Hodgkin's disease by in situ hybridisation. These data show that in Hodgkin's disease HRS cells frequently display polyploidy compared with background cells and are, therefore, probably the only neoplastic component in this disease. Correlations between polysomy and tumour type or grade could not be made from these data owing to the limited number of cases examined and to problems with interpreting data from truncated nuclei.

Adolescent↗
PubMed1997

Can computers improve the Health of the Nation?

In this paper the author considers whether the use of computers can be demonstrated to have a positive impact upon the effectiveness of health screening, in accordance with the Health of the Nation document. It is based upon a study of 1.1 million patients registered with 283 general practices in the North West region of the UK.

Cerebrovascular Disorders↗
PubMed1996

Improving patient care in the UK: clinical audit in the Oxford Region.

This paper is concerned with the effectiveness of clinical audit as the principal quality control and improvement process in the UK National Health Service (NHS). The paper starts by tracing the historical development of clinical audit in the UK within the context of the major management reforms introduced within the NHS in the last ten years. The paper presents the findings of a major study of published audits within the Oxford, Four Counties and Anglia region. This study provides a snapshot of current audit practice and provides the opportunity to test the hypothesis that current practice does not reflect the stated aim of a structured investigation into the quality of patient care leading to a direct improvement in patient care. The paper considers the reasons for the discrepancy between theory and practice. It argues for the need for a structured approach to address some of these issues. The paper outlines a systematic and structured approach to clinical audit which is part of an overall programme of trying to harmonize and improve practice in audit within the Region. It concludes with plans for the future including the development of a dedicated audit tool based around a structured method.

England↗
PubMed1994

Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy.

Glomerular IgA in IgA nephropathy (IgAN) is at least in part polymeric, and is thought to derive from the mucosal IgA system in view of the association between mucosal infection and haematuria in this condition. To investigate this hypothesis, an in situ hybridization (ISH) technique was developed for the detection of J chain mRNA, the expression of which has been correlated with the secretion of high level polymeric immunoglobulin (pIg). Endoscopic duodenal biopsies from ten patients and matched controls were examined by: (i) two color immunofluorescence (IF); (ii) ISH; and (iii) combined ISH and IF, to permit simultaneous identification of plasma cell type. IF revealed a reduction in the percentage of IgA plasma cells (P < 0.02) and increased absolute numbers of IgG cells (P < 0.02) in patient biopsies. ISH demonstrated fewer J chain mRNA expressing plasma cells (P < 0.005) with lower signal intensity (P < 0.002) in patients' biopsies compared with controls. Combined ISH and IF confirmed a reduction in J chain mRNA-positive IgA plasma cells in the patient biopsies (P < 0.02). The reduction in J chain mRNA expression in duodenal IgA plasma cells in IgAN argues against the gastrointestinal lamina propria as the source of glomerular pIgA.

Adult↗
PubMed1994

The effect of adrenalectomy on water permeability in rat papillary collecting duct.

1. Chronic adrenal insufficiency impairs maximal urine concentration, probably in part due to reduced medullary tonicity but also possibly by inhibition of distal nephron water transport. This latter defect has been demonstrated in rabbit but not in rat. 2. Since the time between adrenalectomy and experiment was different in rabbit and rat studies, diffusional water permeability was evaluated in the papillary collecting duct in the absence and presence of submaximal (20 microU/mL) and supramaximal (200 microU/mL) arginine vasopressin (AVP) in adrenalectomized rats at 7, 14 and 21 days. 3. Experimentation 7 days after adrenalectomy failed to demonstrate significantly altered basal or AVP-induced water permeability which increased by 23 and 78% with submaximal and supramaximal concentrations, respectively. Submaximal AVP concentrations also induced a comparable change in water permeability in adrenalectomized rats at 14 days; however, 21 days after adrenalectomy, diffusional water permeability was not increased by 20 microU/mL AVP (3.31 +/- 0.22 to 3.31 +/- 0.24 microns/s). Nevertheless, the effect of a supramaximal AVP concentration (200 microU/mL) was not altered by adrenalectomy (4.54 +/- 0.39 to 8.08 +/- 0.96; P < 0.01). Incubation of collecting ducts in aldosterone for 2 h did not reverse the inhibitory effect of chronic adrenalectomy on AVP-stimulated water transport. 4. These studies suggest that mineralocorticoid withdrawal does impair the hydro-osmotic action of AVP in the rat papillary collecting duct but that this effect takes between 14 and 21 days to occur.

Adrenal Glands↗
PubMed1993

Somatostatin as a modulator of distal nephron water permeability.

1. Experiments in vivo and in vitro were performed in the rat to define the role of somatostatin in modulating the hydro-osmotic action of arginine vasopressin. 2. Somatostatin had a biphasic effect on basal collecting duct diffusional water permeability with 10(-9) mol/l somatostatin producing a 14% reduction in permeability, whereas concentrations of 10(-6) and 10(-5) mol/l significantly increased basal water permeability by 13% and 22%, respectively. Somatostatin (10(-9) mol/l) also inhibited the increase in water permeability produced by arginine vasopressin, although this inhibitory effect was reduced by a 10-fold increase in arginine vasopressin concentration (5 ng/ml). 3. In the anaesthetized water-diuretic rat, low dose somatostatin (60 micrograms/h) increased free water clearance by 23% (P < 0.01), whereas increasing the somatostatin concentration (600 micrograms/h) produced a transitory 40% fall in free water clearance (P < 0.01). As in the experiment in vitro, somatostatin inhibited the action of arginine vasopressin, although a very high concentration of arginine vasopressin (250 ng/h) partly overcame this effect. 4. Glomerular filtration rate and renal electrolyte excretion (sodium, potassium, calcium, magnesium) were not altered by somatostatin, although renal inorganic phosphate excretion was increased. The papillary solute gradient was unaltered by somatostatin. 5. These results suggest that circulating somatostatin may have a physiological role in modulating distal nephron water transport with a low concentration directly inhibiting and a high concentration facilitating water transport. There is also evidence of competitive binding between somatostatin and arginine vasopressin which antagonizes the hydro-osmotic action of arginine vasopressin.

Animals↗
PubMed1993

Hypertension education: patient knowledge and satisfaction.

Education of patients with various diseases, including hypertension, usually occurs at an individual level through a patient's doctor as well as via various media campaigns which also includes general community education. To evaluate their effects, the knowledge of 84 patients with hypertension was evaluated by a simple 13 question true/false questionnaire and the results compared with 58 normotensive subjects matched for sex, age and educational status. A significant difference in knowledge about hypertension could not be elicited between the two groups even when compared for sex or educational status. However, subjects > 70 years of age (hypertensives and controls) demonstrated a lower level of knowledge (P < 0.05). Further questioning of the hypertensive group elicited a high level of satisfaction with their doctor's educational skills (68%) and 57% were satisfied with their own knowledge. Nevertheless, 70% requested more information about their disease. These results suggest a reasonable level of knowledge within the general community presumably reflecting community education programmes. While hypertensive patients were not more knowledgeable under the test conditions, they were reasonably satisfied with their knowledge which they stated came primarily from their doctor. Nevertheless, these findings question the effectiveness of some current patient education initiatives.

Female↗
PubMed1992

Simultaneous in situ hybridisation of native mRNA and immunoglobulin detection by conventional immunofluorescence in paraffin wax embedded sections.

AIMS: The development of a technique for simultaneous in situ hybridisation for native mRNA and conventional immunofluorescence for cytoplasmic antigens in routine pathology specimens. METHODS: Cocktails of synthetic deoxyoligonucleotides coding for immunoglobulin J chain and kappa light chain were 3' end labelled enzymatically with digoxigenin using terminal deoxynucleotidyl transferase. Native mRNA sequences were "unmasked" using proteolytic digestion with proteinase K and hybrid detection was achieved with an alkaline phosphatase labelled anti-digoxigenin antibody. Alkaline phosphatase was visualised with Fast red/naphthol AS-MX phosphate. Fluorescein isothiocyanate (FITC) conjugated anti-isotype antibodies were used simultaneously at the detection stage to identify the isotype production by individual plasma cells in endoscopic duodenal biopsy specimens. RESULTS: The IgA plasma cells of the lamina propria were identified by immunofluorescence and hybrids were detected in the anticipated plasma cell population by Fast red visualisation. The reaction product was visible in bright field or ultraviolet illumination which allowed FITC and Fast red labels to be visualised together under ultraviolet light at 490 nm. Dual labelled cells were clearly visible. Morphology was well preserved throughout. CONCLUSIONS: This technique permits the demonstration of specific mRNA species in cells expressing immunoglobulin. It combines all the advantages of non-radioactive synthetic oligonucleotide probes and conventional immunofluorescence techniques in routine formol-saline fixed and paraffin wax embedded sections with good retention of morphology.

Antigens↗
PubMed1991

Intracatheter streptokinase for recurrent peritonitis in CAPD.

Intracatheter streptokinase (SK) is advocated as effective treatment with minimal adverse effects in both recurrent bacterial peritonitis and catheter fibrin blockage in continuous ambulatory peritoneal dialysis (CAPD) patients. We reviewed 35 instillations in 20 patients noting a high (86%) side effect profile consisting of fever, onset of turbid dialysis effluent and/or abdominal pain. SK probably releases fibrin clot containing bacteria, leukocytes and debris from the colonized catheter into the peritoneal cavity causing a "peritonitis-like syndrome" of 1 to 3 days duration. Fungal peritonitis occurred after SK in 2 patients. Failure of SK therapy was encountered in Staphylococcus epidermidis infection (p less than 0.05 versus other organisms), which may be related to its protective capsular polysaccharide slime and ability to adhere to plastic prosthetic devices. SK, in this study, was useful treatment in relapsing bacterial peritonitis (50% overall cure) but failed to correct catheter malfunction.

Adult↗