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Biomedical subjects

M Small

Publications and source records attributed to M Small.

At least 73 records · Page 4Linked to original sources

Evaluation of glycaemic control limits using the Ames DCA 2000 HbA1c analyser.

The Ames DCA 2000 is a benchtop analyser that measures HbA1c by an agglutination inhibition immunoassay using a monoclonal antibody. Laboratory and nursing staff measured HbA1c on-site in 78 patients with Type 1 diabetes at the outpatient clinic. Significant correlations were noted with both the Corning Glytrac total HbA1 assay (r = 0.89) and the Novoclone assay for HbA1c (r = 0.95). Mean within-assay CV was 1.6% and 3.0% at HbA1c of 5.4% and 13.0%, respectively, while between-assay CVs were 4.2% and 3.8%. These results are as good as our routine laboratory method based on the Corning HbA1 assay. Locally derived reference population data for HbA1c were produced and patients were assigned to categories of good, acceptable, and poor glycaemic control using conventional recommendations for Type 2 diabetes. There was poor agreement between the methods, with only 22% of patients achieving good/acceptable control using the DCA 2000, while 46% of patients had an HbA1 in this range. It appears that the convention for derivation of control limits for HbA1 does not hold for this HbA1c assay.

Antibodies, Monoclonal↗

Denial of illness in stroke.

BACKGROUND: The effects of stroke on classically nondominant hemisphere functions have received less attention than those on the dominant hemisphere, but visuospatial neglect and denial of illness both produce significant morbidity. SUMMARY OF COMMENT: The early literature on denial of illness is discussed and the etiological theories are examined. These are explanations based on deficits of higher mental function, impaired sensory input (especially proprioceptive), an abnormal representation of body image, psychodynamic defense mechanisms, and/or premorbid personality factors. CONCLUSIONS: Denial of illness is an important consequence of stroke. No explanation thus far proposed is entirely satisfactory. The consequences on rehabilitation and strategies for therapy have not been adequately investigated.

Cerebrovascular Disorders↗

Osteoradionecrosis of the petrous bone and recurrent cerebrospinal fluid otorrhoea.

A case is reported of delayed necrosis of the petrous bone following a course of radiotherapy for a well-differentiated squamous cell carcinoma in a 60-year-old female who presented with recurrent intractable cerebrospinal fluid otorrhoea, meningitis and pneumocephalus. Multiple attempts at surgical repair of the necrosed dural deficit and tegmental fistula failed and eventually petrousectomy was necessary leading to a successful outcome.

Carcinoma, Squamous Cell↗

Increased fetal hemoglobin in insulin-treated diabetes mellitus contributes to the imprecision of glycohemoglobin measurements.

An increased prevalence of fetal hemoglobin (HbF) has been described in pediatric insulin-dependent patients. The popular electroendosmotic method for glycohemoglobin includes HbF. In an adult population comprising 50 insulin-treated and 57 non-insulin-treated diabetic patients and 57 control subjects, we measured HbF by HPLC and measured glycohemoglobin by both HPLC and an electroendosmotic method. Of the insulin-treated patients, 46% had concentrations of HbF > or = 0.5%, compared with 25% of non-insulin-treated patients and 23% of controls (P < 0.02). In the insulin-treated patients, the two glycohemoglobin methods correlated best when the HPLC measurements included HbF (r = 0.92 vs r = 0.84). Fructosamine concentrations correlated best with glycohemoglobin concentrations determined by methods that accounted for HbF. The true between-batch CV of the electroendosmotic assay increased (from 4.33% to 8.33%) when variable interpatient HbF concentrations were included. Thus, HbF must be considered when interpreting glycohemoglobin measured by an electroendosmotic method and when comparing it with other measures of glycemic control.

Adolescent↗

Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture.

We have investigated the ability of a heterogeneous thymic stromal cell (HTSC) culture system to promote in vitro differentiation of CD3-4-8- thymocytes. Culture of purified murine CD3-4-8- thymocytes on HTSC for 1 d resulted in the appearance of CD4+8+ cells, which did not occur when the sorted cells were maintained in medium alone. It is remarkable that when the culture period was extended to 2 d, CD3-4-8- progenitors differentiated further to CD4+8- and CD4-8+ cells, which also expressed high levels of TCR-CD3. This rapid differentiation on stroma in vitro appears to outpace parallel development in vivo. The differentiation potential of a subset of CD3-4-8- thymocytes that express high levels of a marker of normal and neoplastic thymic progenitors, the 1C11 antigen, was examined next. 1C11hiCD3-4-8- cells also gave rise to CD4-8+ and CD4+8+ populations after 1 d of culture on HTSC. Extending the culture period to 2 d resulted in a significant percentage of CD3-expressing cells that were CD4+8+, CD4+8- and CD4-8+ cells. These results suggest that in the in vitro HTSC culture system, various subsets of immature thymocytes can differentiate into all the mature phenotypes of cells normally found in the adult mouse thymus. This may provide a novel and rapid assay for thymic progenitors.

Animals↗

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria.

OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.

Adult↗

An 'empty' sphenoid mucocele.

Sphenoid sinus mucoceles behave as mass lesions producing erosion of adjacent bone and cranial nerve palsies. The probable cause is obstruction of the ostia of the sinus. We describe a case which was 'cured' inadvertently by a nasal polypectomy.

Aged↗

Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects.

Adenylate cyclase activity and levels of guanine nucleotide regulatory proteins (G-proteins) were compared in platelets from normal and non-insulin-dependent diabetic (NIDDM) male subjects. Whilst no differences were noted in basal and NaF-stimulated adenylate cyclase activities the degree of stimulation achieved by both forskolin and prostaglandin, E1 was lower by some 34 and 52% respectively, in platelet membranes from diabetic subjects compared with those from normal control subjects. Altered alpha 1-adrenoceptor-mediated inhibition of prostaglandin E1-stimulated adenylate cyclase activity was evident; it being some 34% lower in platelet membranes from diabetic subjects compared to controls. Analysis of G-protein alpha-subunits, using specific anti-peptide antisera, showed that platelets from all subjects exhibited the Gi-2 and Gi-3, but not the Gi-1 forms of the inhibitory G-protein 'Gi' and all expressed the 42 kDa species of alpha-subunit of the stimulatory G-protein Gs. Whilst platelets of diabetic subjects had levels of Gs which were comparable to those found in control subjects their levels of Gi-2 and Gi-3 were some 49 and 75%, respectively, of those found in platelets from control subjects. It is suggested that changes in adenylate cyclase functioning and G-protein expression may contribute to altered platelet functioning in non-insulin-dependent diabetic subjects.

Adenylyl Cyclases↗

Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects.

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.

Acute Disease↗

Do rheological variables play a role in diabetic peripheral neuropathy?

Whole blood viscosity and its determinants were measured in diabetic patients with and without peripheral neuropathy to assess whether these variables could have a role in the microvascular aetiology of diabetic peripheral neuropathy. Although corrected whole blood viscosity at high and low shear rates (5.29 +/- 0.51 and 21.10 +/- 3.03 mPa s), plasma viscosity (1.41 +/- 0.13 mPa s), and red cell filtration ratio (0.49 +/- 0.04) in diabetic patients were significantly different from non-diabetic control subjects (high shear rate 4.83 +/- 0.54, low shear rate 17.36 +/- 2.78, plasma 1.29 +/- 0.09 mPa s, all p less than 0.001, and red cell filtration ratio 0.55 +/- 0.03, p less than 0.001) there were no significant differences between diabetic patients with neuropathy and those without. Blood rheology is altered to a similar extent in diabetic patients with and without neuropathy.

Blood Viscosity↗

Screening for hyperlipidaemia in diabetes mellitus. Relationship to glycaemic control.

Diabetic patients have an increased risk of developing cardiovascular disease which, in part, may be due to lipid abnormalities. Our aim was to establish from an initial screening programme what proportion of diabetic patients attending a routine diabetic outpatient clinic had hyperlipidaemia despite having good or acceptable glycaemic control. We screened 299 randomly selected diabetic patients to assess the prevalence of hyperlipidaemia and its relationship to glycaemic control. Twenty-eight per cent had hyperlipidaemia (defined as cholesterol greater than 6.5 mmol/L and/or non-fasting triglycerides greater than 3 mmol/L). Of these hyperlipidaemic patients, 71% had good or acceptable glycaemic control as defined by a glycated haemoglobin value of less than 10%. Approximately 40% of type 2 diabetic patients had body mass index values outside recommended targets indicating the potential of weight reduction in this group as a treatment modality. Our results indicate that the majority of hyperlipidaemic diabetic patients had good or acceptable glycaemic control, and as such these patients are potential candidates for specific lipid lowering therapy.

Adolescent↗

The role of the polyol pathway in diabetes mellitus.

The mechanism by which hyperglycaemia leads to diabetic complications has not been fully elucidated. Non-enzymatic glycosylation leads to considerable functional and structural alteration of proteins. Hyperglycaemia also induces changes in intracellular metabolites, particularly in the polyol pathway. Aldose reductase inhibitors, which block the polyol pathway, have been shown to prevent complications in animal models, and this provides the rationale for the large scale trials that are presently being conducted.

Aldehyde Reductase↗

Serial studies of evoked potentials and circulating lymphocyte subsets for multiple sclerosis: attempts to monitor progress.

A concurrent change in evoked potential measurements and quantitation of circulating T-suppressor (CD8) lymphocyte subpopulations might indicate increased subclinical disease activity. Eight untreated patients with clinically definite multiple sclerosis were monitored monthly for changes in the numbers of cells positive for CD8 markers, and hence in the ratio of CD4: CD8 positive cells. Such changes were found not to be associated with changes in evoked potentials or clinical status.

Adult↗

Radio-necrosis of the temporal bone presenting as cerebellopontine angle lesion.

We report a case of osteoradionecrosis of the temporal bone which presented with symptoms and signs of cerebellopontine angle lesion. The clinical, radiological, histological and bacteriological findings are reported. The occurrence of osteoradionecrosis of the temporal bone and the factors which predispose to it are discussed with particular emphasis on the time lapse between radiotherapy and its development. This presentation has not previously been reported.

Bone Diseases↗

Plasma and dialysate levels of pefloxacin and its metabolites in CAPD patients with peritonitis.

Six patients with acute peritonitis undergoing continuous ambulatory peritoneal dialysis for end-stage renal failure received an 800 mg loading dose of pefloxacin mesylate orally followed by 400 mg twice daily orally for 10 or 21 days. Plasma and dialysate levels of both pefloxacin and its metabolites were measured. Plasma levels in excess of the MIC for all infective bacteria were achieved within 90 min and in dialysate within 4 h. No significant accumulation of pefloxacin or its metabolite norfloxacin was noted. However, both serum and dialysate levels of the metabolite pefloxacin N-oxide rose continuously during treatment. Plasma and dialysate levels of all three agents fell rapidly during the five days after treatment had stopped. No major side effects were observed, although two patients developed Achilles tendonitis.

Adult↗