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Biomedical subjects

E J Dunn

Publications and source records attributed to E J Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to determine the influence of type 2 diabetes on fibrinolysis by assessing interactions between the regulatory components of fibrinolysis and the fibrin clot, using fibrinogen purified from 150 patients with type 2 diabetes and 50 matched controls. METHODS: Clot lysis rates were determined by confocal microscopy. Plasmin generation was measured using a plasmin-specific chromogenic substrate. Surface plasmon resonance was used to determine the binding interactions between fibrin, tissue-type plasminogen activator (t-PA) and Glu-plasminogen; cross-linkage of plasmin inhibitor to fibrin by factor XIII was determined using a microtitre plate assay. RESULTS: Lysis of diabetic clots was significantly slower than that of controls (1.35 vs 2.92 microm/min, p<0.0001) and plasmin generation was significantly reduced. The equilibrium binding affinity between both t-PA and Glu-plasminogen and fibrin was reduced in diabetic subjects: t-PA, K (D)=0.91+/-0.3 micromol/l (control subjects), 1.21+/-0.5 micromol/l (diabetic subjects), p=0.001; Glu-plasminogen, K (D)=97+/-19 nmol/l (control subjects), 156+/-66 nmol/l (diabetic subjects), p=0.001. Cross-linkage of plasmin inhibitor to fibrin by factor XIII was enhanced in diabetic subjects, with the extent of in vitro cross-linkage correlating with in vivo glycaemic control (HbA(1c)) (r=0.59, p=0.001). CONCLUSIONS/INTERPRETATION: These results indicate that impairment of the fibrinolytic process in diabetic patients is mediated via a number of different mechanisms; these may be a consequence of post-translational modifications to fibrinogen molecules, resulting from their exposure to the abnormal metabolic milieu associated with diabetes.

Aged↗
PubMed2005

The influence of type 2 diabetes on fibrin structure and function.

AIMS/HYPOTHESIS: The precise mechanisms underlying the increased risk of cardiovascular disease (CVD) in type 2 diabetes are unclear. Fibrin clot structure has been related to CVD risk in the general population. We therefore assessed this in type 2 diabetic patients as a potential mechanism whereby diabetes influences CVD risk. METHODS: Fibrin clots were formed from fibrinogen purified from 150 subjects with type 2 diabetes and varying degrees of glycaemic control (assessed by HbA1c), and from 50 matched control subjects. Clot structure was assessed by turbidity, permeation and confocal microscopy. The specific effect of glucose itself was assessed by analysing the structure of clots formed from purified fibrinogen in the presence of increasing concentrations of the sugar. RESULTS: Clots formed by fibrinogen purified from type 2 diabetic subjects had a denser, less porous structure than those from control subjects. The structural changes found were related to the individual's glycaemic control; HbA1c correlated negatively with permeation coefficient (Ks) values (indicates clot pore size) (r = -0.57, p < 0.0001) and positively with maximum absorbance (indicator of fibre size) (r = 0.33, p < 0.0001), branch point number (r = 0.78, p < 0.0001) and fibre density (r = 0.63, p < 0.0001). The ambient glucose level influenced clot structure; hypo- (< 5 mmol) and hyperglycaemia (> or = 10 mmol/l) were both associated with a reduction in Ks values and maximum absorbance, and with increased fibre density and branch point number within clots. CONCLUSIONS/INTERPRETATION: The structural differences found to occur in type 2 diabetes and in association with hypo- and hyperglycaemia may confer increased resistance to fibrinolysis, and in consequence contribute to the increase in CVD risk in diabetic patients.

Blood Coagulation↗
PubMed2005

Effect of 902 MHz mobile phone transmission on cognitive function in children.

We examine whether a standard mobile exposure at 902 MHz has a significant effect on cognitive function in 18 children 10-12 years of age. These were in a single group in which each child was given a single training session and then three test sessions in a randomized, three-way crossover design, using the cognitive drug research (CDR) cognitive assessment system. Exposures were 0, 0.025, or 0.25 W from a standard Nokia 3110 mobile phone handset mounted on a plastic headset in normal use position. The results of testing showed that the baseline (0 W) performance for the reaction time measurements was considerably slower than for the comparable measures in adult. There was a tendency for reaction time to be shorter during exposure to radiation than in the sham (baseline) condition, an effect that was most marked for simple reaction time. However, no effects reached statistical significance after Bonferroni correction. Therefore, we conclude that this study on 18 children did not replicate our earlier finding in adults that exposure to microwave radiation was associated with a reduction in reaction time. It should be noted that the present study investigated the effects of radiation from a GSM handset, whereas in our previous study the effect on reaction time was observed only with a more powerful analogue handset.

Body Burden↗
PubMed2005

Type 2 diabetes: an atherothrombotic syndrome.

Insulin resistance is found in around 80-90% of subjects with older onset (type 2) diabetes and in approximately 25% of the general population. Insulin resistance prior to the development of frank type 2 diabetes and type 2 diabetes itself is associated with a significant increase in the risk of atherothrombotic disease, which is due in part to a disruption in the balance of factors regulating coagulation and fibrinolysis. Both insulin resistance and type 2 diabetes are associated with the development of endothelial dysfunction, and enhanced platelet aggregation and activation. Whilst the plasma levels of many clotting factors including fibrinogen, FVII, FVIII, FXII, FXIII b-subunit are elevated, the fibrinolytic system is relatively inhibited as a consequence of an increase in plasminogen activator inhibitor type-1 (PAI-1) levels. These changes favour the development of a hypercoagulable pro-thrombotic state, which may in turn enhance cardiovascular risk by increasing the likelihood of developing an occlusive thrombus within a coronary/cerebral artery, and/or contributing to the development of atherosclerotic lesions. This article reviews the current published evidence of the pro-thrombotic changes that occur in association with type 2 diabetes and insulin resistance, and the putative underlying mechanisms which lead to these changes.

Animals↗
PubMed1999

Can intensive treatment alter the progress of established diabetic nephropathy to end-stage renal failure?

Diabetic nephropathy is now the leading cause of end-stage renal disease in the Western world, and is associated with a higher patient morbidity and mortality than other causes of renal failure, largely because of associated cardiovascular disease. Numerous studies have elucidated the factors which influence its onset and progression. The St Vincent Declaration in 1994 proposed standards for the appropriate management of patients with diabetic nephropathy. We assessed whether referral to a nephrology clinic attempting to apply these standards influenced the progression of diabetic nephropathy. The results show a significant improvement in blood pressure, glycosylated haemoglobin and serum cholesterol following referral. There was a significant reduction in the rate of decline of renal function following referral in 39% of patients. With the possible exception of diabetic control there were no significant differences in the management of those that did and did not show improvement. The results show that with intensive out-patient clinic monitoring it is possible to improve the quality of patient care, and that even in established diabetic nephropathy it is possible to slow the rate of progression to end-stage renal failure.

Adult↗
PubMed1999

The care of patients with diabetic nephropathy: audit, feedback, and improvement.

Diabetic nephropathy is the commonest cause of end-stage renal failure in the developed world. The quality of care of 152 patients with diabetic nephropathy was assessed at the time of referral to a single nephrologist. The type II diabetics (62%) were older than the type I diabetics (38%) (mean 65 years vs. 48 years). The mean duration of diabetes was 17 years. Significant cardiovascular disease was present in 52%. There was diabetic retinopathy in 84% of the type I diabetics and 53% of the type II diabetics. Overall, 63% had hypertension at referral (St Vincent Declaration criteria), untreated in 25%. ACE inhibitors were not prescribed in 48% when no contraindications to their use were present. Glycosylated haemoglobin was > 9.1% in 29%. Twenty were prescribed medications inappropriate to their renal function. Of patients with ischaemic heart disease and serum cholesterol > 5.5 mmol/l, 82% were untreated; 82% of patients with secondary hyperparathyroidism were also untreated. At initial referral, many patients' care was sub-optimal. Referral was too late for adequate preparation for renal replacement therapy in 33%. Following a process of education and feedback of the results to referring practitioners, the timing of referral improved. We emphasize the need for closer co-operation between those managing diabetic patients with nephropathy to optimize their care.

Adult↗
PubMed1999

Metastatic disease of the cervical spine. A review.

The treatment of cervical metastatic disease requires a multidisciplinary team approach to evaluation and management and demands consideration of multiple factors before a regimen is accepted. The patient's overall functioning and medical status, life expectancy, history of treatment, tumor type, and location within the cervical spine and individual vertebrae all must be evaluated carefully. The majority of lesions will be amenable to nonoperative aggressive modalities aimed at shrinking tumor size and halting growth. Surgical intervention is limited to specific indications, including spinal instability, progressive neurologic deterioration from bony collapse and compression, intractable pain, and failure of conservative means of treatment.

Cervical Vertebrae↗
PubMed1999

Variation in the posterior vertebral contour line at the level of C-2 on lateral cervical roentgenograms: a method for odontoid fracture detection.

As an aid to the assessment of alignment and lordosis, four contour lines can be drawn on the lateral radiograph of the cervical spine. One of these contour lines is the posterior vertebral contour line, in which a smooth, gentle curve, convex anteriorly, is formed by a line drawn along the posterior margins of the cervical vertebral bodies. It is unknown whether discontinuity in the posterior contour line at this level represents a pathologic process of the odontoid. We analyzed the posterior cortex of C-2 and the odontoid in 500 lateral cervical spine radiographs to determine the amount of step-off (deviation from the posterior contour line) seen in normal lateral cervical roentgenograms. Only 15% (n = 75) showed any step-off; none exceeded 3 mm. We recommend that patients presenting with a history of cervical spine trauma who have a step-off at the posterior contour line at the odontoid/C-2 level of > or =3 mm should have fine-cut tomography or multiplanar computed tomography scanning to further assess the odontoid process and rule out fracture.

Adolescent↗
PubMed1990

Sternotomy infection: poor prediction by acute phase response and delayed hypersensitivity.

Two hundred twenty-one consecutive adult cardiac surgical patients were examined prospectively for nutritional protein state, acute phase protein response, and delayed hypersensitivity reaction in an attempt to identify patients at high risk for the development of sternal wound infection, which occurred in 6 patients (2.7%). There was no significant correlation between preoperative nutritional protein concentrations (retinol-binding protein, prealbumin, and transferrin) and acute phase protein levels (C-reactive protein, alpha 1-acid glycoprotein, and complements B and C3), nor a statistically significant relationship between nutritional state or acute phase protein response and the development of sternal infection. Preoperative complement C3 levels were elevated, however, in 80.0% of those in whom sternal infections developed compared with 30.6% of those with well-healed wounds. Similarly, postoperative concentrations of alpha 1-acid glycoprotein were elevated in 80.0% of those in whom sternal infections developed compared with 28.6% of those with well-healed wounds. There was no correlation between delayed hypersensitivity and the risk of sternal infection, nor between preoperative nutritional protein and acute phase protein values. Seventy-three percent of patients were anergic on postoperative day 2. Stepwise logistic regression showed that age, body weight, preoperative intensive care unit stay, repeat median sternotomy, internal mammary artery grafting, postoperative hemorrhage, and postoperative cardiac arrest correlated with the development of sternal infection, whereas transfusion requirement, reexploration for bleeding, and the operation performed did not. We conclude that routine delayed hypersensitivity testing is of no value in predicting high-risk cardiac surgical patients when the anergy battery is placed on the preoperative day. Although statistically insignificant, possibly due to the small number of patients in whom sternal infection developed in this study (type II error), a larger study might find preoperative complement C3 and post-operative alpha 1-acid glycoprotein levels to be predictive of patients at risk for the development of sternal wound infection. The final logistic model for the predicted risk 2%) of sternal wound infection is: PREDSWC = exp(EQ)/1 + exp(EQ) where EQ = (0.38 x age) + (0.24 x weight) + (5.42 x preop ICU) + (4.39 x redo) + (7.14 x IMA) + (4.49 x hemorrhage) + (8.81 x arrest) - 62.72, and where preop ICU, redo, hemorrhage, and arrest are defined as yes (1) or no (0), IMA-is defined as 0, 1, or 2, age is in years, and weight is in kilograms.

Acute-Phase Proteins↗
PubMed1990

Surgical implications of sclerosing mediastinitis. A report of six cases and review of the literature.

Sclerosing mediastinitis is an uncommon disease associated with a multiplicity of clinical syndromes. The cause of this disorder is probably an abnormal fibroproliferative response to an inflammatory stimulus, most commonly a granulomatous infection secondary to Histoplasma capsulatum. The pathophysiology of this disease is predicated on the encasement of mediastinal vital organ structures within a dense fibrotic mass. This mass appears to emanate from an invasive chronic inflammatory process causing erosion as well as external compression of these structures. The following case reports illustrate the diversity of this disease entity, representing a patient population from the Ohio River Valley, endemic for histoplasmosis. The purpose of this report is to elucidate the various clinical manifestations of sclerosing mediastinitis and to correlate the pathologic process with a rational approach to treatment.

Adult↗
PubMed1990

The relation of the Halstead-Reitan neuropsychological battery to functional daily living skills in geriatric patients.

This study investigated the nature of the relationship between neuropsychological tests, the Halstead-Reitan Battery, and a measure of everyday living ability, the Community Competence Scale. The sample consisted of 40 geriatric patients referred for suspected dementia. The results indicated that neuropsychological tests were moderately predictive of measures of functional daily living skills. Although some specific neuropsychological measures, or combination of measures, were more predictive of particular functional daily living skills, their relationship did not necessarily follow logical or theoretical expectations. Thus, while it may be safe for neuropsychologists to make predictions about a patient's global capacity to function independently, predictions regarding specific functional daily living skills may be unwarranted.

Journal Article↗
PubMed1990

Fracture of the occipital condyle: case report and review of the literature.

Fracture of the occipital condyle is a rare injury. We report a patient with an occipital condyle fracture who presented with negative plain films and a cranial nerve palsy. Diagnosis was established with high-resolution computed tomography. This fracture should be considered in a trauma patient with neck pain, negative plain cervical spine radiographs, and a cranial nerve palsy.

Accidents↗
PubMed1989

The sensitivity of the Bender-Gestalt Test as a screening instrument for neuropsychological impairment in older adults.

We investigated the sensitivity of the Bender (1938) Visual-Motor Gestalt Test (BGT) using the Halstead-Reitan Neuropsychological Battery (HRB) as the criterion for cortical dysfunction. We studied 95 subjects over age 55 who had been diagnosed as having dementia or pseudodementia. Subjects were classified as mild, moderately, or severely impaired on the HRB and as impaired or unimpaired on the BGT. The results indicated that the BGT is less sensitive (36%) than was expected when used on an impaired geriatric population. The data further indicated that false negatives occurred more frequently with the BGT when individuals had mild neuropsychological impairment. Less frequent misclassifications occurred as the severity of impairment on HRB indices increased.

Aged↗
PubMed1989

Correlation of two competence assessment methods in a geriatric population.

A 10-subscale version of the Community Competence Scale, a structured interview, and the Scale of Competency in Independent Living Skills, a rating scale completed by a relative, were administered to 40 geriatric patients with suspected dementia. While the two assessments of competence appear to examine a common global domain, individual correlations between subscales of the two measures were only moderate. The findings provide limited support for the construct of competence.

Activities of Daily Living↗
PubMed1989

Relation of cognitive functioning to daily living skills in a geriatric population.

A modified version of the Community Competence Scale was administered along with the Wechsler Adult Intelligence Scale--Revised (WAIS--R) to 40 geriatric patients with suspected dementia. Scores on the Competence Scale, a measure of functional daily living skills, were correlated .72 with Full Scale IQs and .77 with Verbal IQs and moderately correlated (.55) with Performance IQs. A number of significant correlations were found between WAIS--R subtests and subscales of the competence instrument. Means and standard deviations for the 10 Competence subscale and total scores are presented.

Activities of Daily Living↗
PubMed1988

Prosthetic replacement surgery for cervical spine metastasis.

Since 1972, 18 patients suffering from metastatic cancer in the cervical spine were treated with prosthetic replacement surgery. The surgery enabled the authors to decompress the spinal cord and the nerve roots and at the same time restore stability in the affected spine. Patients suffering from severe pain and spinal cord and/or nerve root compression secondary to involvement of a single vertebral body particularly benefited from this surgery. The rates of positive recovery were as follows: 94.1% for pain relief, 91.7% for motor recovery, and 87.5% for ambulation. The surgical efficacy was maintained until the terminal stage. Tumor recurrence took place in five cases--two anterior, and three posterior. Anterior recurrence caused a marked instability, whereas posterior recurrence did not affect stability.

Cervical Vertebrae↗