Biomedical subjects
Publications and source records attributed to M Small.
C-reactive protein concentrations as a marker of inflammation predicts vascular risk and is raised in type-2 diabetes. In a 6-month double-blind placebo controlled trial, a combination of transdermal oestradiol 80 microg with continuous oral norethisterone 1 mg significantly reduced C-reactive protein concentrations in postmenopausal women with type-2 diabetes.
In thirteen patients with prominent visuospatial hemineglect following acute right hemisphere cerebrovascular accident (CVA) and in two normal controls we investigated bisection of horizontal lines at various viewing distances. Their task was to indicate the centre of each horizontal line using a hand-held laser pointer. In five of the thirteen patients the angular error was greater for lines further away than for lines of identical angular size within reaching distance, confirming previous results [Cowey, A., Small, M., Ellis, S., Visuospatial neglect can be worse in far than in near space. Neuropsychologia, 1994, 32, 1059-1066]. There was no evidence that a sudden increase in the angular displacement occurred when the maximum reaching distance was exceeded.
In twelve patients with left visuospatial hemineglect following acute right hemisphere cerebrovascular accident (CVA), and in twelve normal controls, we used a matching task to investigate judgement of the length of lines. Their task was to choose which of three lines of different length matched a separate single line. On each trial, the lines were all vertical or all horizontal. The set of three lines was presented either to the left or the right of the single line. When the lines were vertical, the choices made both by normal subjects and patients were nearly always correct. However, when the lines were horizontal and the set of comparison lines was on the left, patients mostly selected a line that was longer than the sample on the right, and never chose shorter lines, suggesting that the length of horizontal lines on the left was underestimated. When the set of three lines was on the right, patients chose the correct line more often, but made errors in both directions, i.e. longer or shorter, although shorter lines were chosen more often than longer lines. The rare errors made by normal subjects were in the same directions as those observed in the patients. The results provide further evidence for a non-Euclidean distortion of perceptual space in patients with left sided visuospatial neglect, and suggest that this distortion could be a gross exaggeration of normal performance or a product of diminished spatial attention, or both.
AIMS: The association of the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene with cardiovascular disease and diabetic nephropathy remains a controversial issue. This review aims to give an overview of the research to date assessing the impact of the ACE polymorphism in Type 1 and Type 2 diabetes mellitus (DM). METHODS: A systematic review of the literature was performed in the databases of MEDLINE, PubMed and EMBASE for the key words 'diabetes mellitus', 'diabetic nephropathy', 'ACE polymorphism' and 'genotype' and relevant articles were considered. RESULTS: A meta-analysis assessing the influence of the ACE polymorphism on disease susceptibility demonstrated significant odds ratios in individuals with the DD genotype for coronary heart disease, myocardial infarction and both diabetic and nondiabetic renal disease. No association was found for left ventricular hypertrophy or hypertension in nondiabetic subjects. CONCLUSIONS: The ACE polymorphism appears to have a significant impact on the progression of diabetic nephropathy and may have therapeutic implications for identifying those individuals resistant to the effects of ACE inhibitors. It also appears to be indicative of an increased vascular risk in diabetic patients; however, larger prospective studies are required to clarify this situation.
We describe an analysis of dynamic behavior apparent in times-series recordings of infant breathing during sleep. Three principal techniques were used: estimation of correlation dimension, surrogate data analysis, and reduced linear (autoregressive) modeling (RARM). Correlation dimension can be used to quantify the complexity of time series and has been applied to a variety of physiological and biological measurements. However, the methods most commonly used to estimate correlation dimension suffer from some technical problems that can produce misleading results if not correctly applied. We used a new technique of estimating correlation dimension that has fewer problems. We tested the significance of dimension estimates by comparing estimates with artificial data sets (surrogate data). On the basis of the analysis, we conclude that the dynamics of infant breathing during quiet sleep can best be described as a nonlinear dynamic system with large-scale, low-dimensional and small-scale, high-dimensional behavior; more specifically, a noise-driven nonlinear system with a two-dimensional periodic orbit. Using our RARM technique, we identified the second period as cyclic amplitude modulation of the same period as periodic breathing. We conclude that our data are consistent with respiration being chaotic.
The Diabetes Control and Complications Trial (DCCT) has provided objective evidence for desirable glycaemic control in Type 1 patients and defines the benefits of good glycaemic control in terms of haemoglobin A1c (HbA1c) values. However, HbA1c assays vary, leading to suggestions that glycaemic control be classified according to numbers of standard deviations (SD) from a local non-diabetic population mean. We have classified the glycaemic control of 339 UK Type 1 diabetic patients (182 male, 157 female, median age 36 (range 15-74) years) using the DCCT to set HbA1c targets and compared this with the SD method. Using age matched controls (mean HbA1c 4.02%, SD 0.28%, n=106), SD guidelines classified 1% of patients into good (HbA1c <3SD from reference mean), 4% into borderline (3-5SD) and 95% into poor (>5SD) glycaemic control. When calibrating the same instrument to the DCCT analyser (r=0.996), 37% of patients had HbA1c results lower than the 7% median value found in the intensively treated DCCT group, while only 12% of patients had values greater than the 9% conventionally treated median HbA1c. DCCT subjects with HbA1c values of less than 8% belonged predominantly to the intensively treated group. In this study, 71% of patients fell into this category. Thus, guidelines based on numbers of SD away from a non-diabetic mean may overestimate the glycaemic control required to reduce microvascular complications in Type 1 patients. Standardizing to DCCT targets is more appropriate.
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We report an unusual case of an extravasation mucocele complicating superficial parotidectomy. The tumour excised was a Warthin's tumour. Three months following the primary surgery a cystic lesion appeared in the parotid bed. It was initially thought to represent a recurrence. The area was re-explored and a mucocele excised. The pathogenesis of mucoceles and the difficulties encountered when dealing with parotid tumour recurrence are discussed.
Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.
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Age-related decline of the thymus in ICR female mice was studied following long-term (three month) weekly exposure to hydrocortisone acetate. When examined one week after cortisone injections, the well-known thymic atrophy was observed. Five weeks after 12 hydrocortisone injections, the cortical volume fraction (Vc), cortical/medullary ratio (C/M), the number of thymocytes and CD4/CD8 profiles were in the range that characterizes younger mice, compared with PBS-injected mice, uninjected controls, or mice given a single hydrocortisone injection 5 weeks earlier. It seems as if thymic involution with age was suspended during the period of glucocorticoid exposure.
Serum insulin concentrations have been used as markers of insulin resistance in population studies examining the relationship between insulin resistance and blood pressure, but the relationship is variable among studies. We hypothesized that differences in cross-reactivity of insulin assays with proinsulin and its split/des-amino products might account for the variation. We therefore examined fasting and post-glucose load serum insulin concentrations (determined by both specific and conventional assays), insulin sensitivity (measured by the euglycaemic clamp technique), and blood pressure, in a group of 56 diabetic (NIDDM) and non-diabetic subjects. Insulin concentrations as measured by the two methods were highly correlated (r = 0.97, p < 0.0001), and the relationships among serum insulin concentrations, insulin sensitivity and blood pressure were independent of assay method; for example, in non-diabetic subjects the univariate correlation between log10AUC insulin and insulin sensitivity index was similar with both methods [r = -0.81 vs. r = -0.82, p < 0.0001 (specific vs. conventional assay)]. Discrepancies between studies in the relationship between serum insulin concentrations and blood pressure are unlikely to be due to cross-reactivity of conventional insulin assays with proinsulin-like molecules.
BACKGROUND AND PURPOSE: Previous studies of lesion localization in dental of hemiplegia have often been confounded by factors such as the cerebral etiology, which aspects of the disorder are denied, and whether delusions are present. Our investigation focuses on denial of hemiplegia, without concomitant delusions, after cerebrovascular accident (CVA). METHODS: The CT scans of 30 patients with denial of hemiplegia after acute stroke were compared with those from 10 CVA patients with hemiplegia and visuospatial neglect but no denial. Lesion sites were detailed using the templates of Damasio and Damasio and, for the deep structures, those of Talairach and Tournoux. RESULTS: Analysis of the CT scans demonstrated that 26 of 30 denial patients had unilateral right-sided lesions and that this group showed a significantly higher incidence of lesions in deep white matter and the basal ganglia. CONCLUSIONS: The results are discussed in relation to recent ideas regarding the role of the basal ganglia and subcortical circuits in movement and executive function.
The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes.
Septic cavernous sinus thrombosis is a serious infective condition with a high mortality and morbidity. We report the first case to our knowledge of septic cavernous sinus thrombosis following manipulation of fractured nasal bone under general anaesthesia. The patient later developed complications of pneumonia with pleural effusion, a vegetative lesion of the mitral valve, and blindness.
CD3-4-8- interleukin-2 receptor positive (IL-2R+) thymocyte precursors from adult mice were cocultured with thymic stromal cells from syngeneic adult mice. The IL-2R+CD3-4-8- thymocytes were obtained by positive panning of IL-2R+ cells followed by either sorting or negative panning of triple negative cells, and they were cocultured with primary or secondary cultures of heterogeneous thymic stromal cells. Phenotypic maturation of these precursor cells was extremely rapid. Within 2 1/2 days significant numbers of CD4+8+ and CD3+4+8- cell populations developed, the latter expressing the alpha beta T-cell receptor (alpha beta-TCR). Thus heterogeneous stromal cell cultures support the development of IL-2R+ precursors and with these methods it will now be possible to isolate the particular stromal cells involved at each stromal-dependent step.
To investigate the discrepancy in the assessment of glycaemic control using glycated haemoglobin (HbA1C) and glycated proteins (fructosamine), the effect of age on these variables was measured in non-diabetic individuals. In 232 non-diabetics, there was a linear relationship between HbA1C and age (r = 0.49, p < 0.0001). Mean HbA1C rose from 3.82% to 4.44% between the ages of 20 and 70. Consequently, when Type 2 diabetic patient samples (n = 128, median age 63 years) were classified according to European guidelines into good or poor glycaemic control using both an age-matched (n = 101) and a younger (n = 108, median age 37 years) non-diabetic reference population, fewer patients were in good control (14% vs. 25%) and more in poor control (73% vs. 53%) when the younger reference population was used (both p < 0.05). In a subgroup of 126 non-diabetic subjects, HbA1C rose with age (r = 0.48), but serum fructosamine and fasting glucose did not (r = 0.07, r = 0.009, respectively, p = NS). Age-associated differences in non-diabetic HbA1C values may affect the assessment of glycaemic control in diabetic patients. It may also partly explain discrepancies found when comparing fructosamine with HbA1C as a measure of glucose control. Age-related HbA1C reference intervals may therefore be required for the treatment of patients and the accurate auditing of clinic performance.
A comprehensive study of denial of hemiplegia, with tests chosen to cover the varied proposed hypotheses, was undertaken. Twenty patients with denial of hemiplegia following acute CVA were studied. Their results were compared with those from two patient 'control' groups. A neurological examination and neuropsychological assessment were carried out in all patients and CT brain scan performed in 21 CVA cases. The findings are discussed in relation to previously proposed theories of causation concerning denial of hemiplegia which include personality factors, cognitive ability and the presence/absence of neurological deficits. CT scan analyses showed that patients with denial of hemiplegia have significantly more white matter involvement, particularly the corona radiata, than those with neglect and there was also a trend that patients with denial are more likely to have lesions in the caudate.