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Biomedical subjects

K Stanton

Publications and source records attributed to K Stanton.

At least 19 recordsLinked to original sources
PubMed2005

Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria.

AIMS: Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL-cholesterol levels. Lipid-lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non-lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients. METHODS: In a double-blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were measured. RESULTS: Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001), and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted (R2) 0.41, P = 0.02). CONCLUSION: Atorvastatin improves endothelium-dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.

Adolescent↗
PubMed2001

Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria.

AIMS/HYPOTHESIS: We examined whether endothelial function is impaired in patients with Type I (insulin-dependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. METHODS: Endothelial function, measured as post-ischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitrate-mediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. RESULTS: Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 +/- 0.3%) compared with normoalbuminuric diabetic patients (5.4 +/- 0.6%) and control subjects (7.9 +/- 0.6%, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 +/- 1.1% vs 20.0 +/- 1.2%, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). CONCLUSION/INTERPRETATION: Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease.

Adolescent↗
PubMed2001

The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes.

OBJECTIVES: The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS: Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed2001

Effect of hydroxyethyl starch on coagulopathy in a swine model of hemorrhagic shock resuscitation.

BACKGROUND: Hydroxyethyl starch (HES) has a known dose-dependant effect on coagulopathy. The purpose of this study was to determine the effect of HES on coagulopathy after a period of hemorrhagic shock. METHODS: Anesthetized swine underwent a 15-minute, 40% blood volume hemorrhage (28 mL/kg) and a 1-hour shock period, followed by resuscitation with sham resuscitation (group I); 6% HES, 15 mL/kg (group II); 5% albumin, 15 mL/kg (group III); lactated Ringer's solution, 39 mL/kg, and 6% HES, 15 mL/kg (group IV); and lactated Ringer's solution, 39 mL/kg, and 5% albumin, 15 mL/kg (group V). Coagulation function was measured by bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, platelet count, and thromboelastography. RESULTS: Platelet counts decreased significantly (p < 0.05) in all resuscitation groups except the sham resuscitation group. A significant decrease in platelets, fibrinogen levels, and maximum amplitude on thromboelastography was related to a dilutional effect of the fluid given and not a result of HES at the dose tested. CONCLUSION: The linear dose-related coagulopathic effects of HES when given at moderate doses does not seem to be worsened by prolonged periods of hemorrhagic shock. The coagulopathy seen during resuscitation from hemorrhagic shock seems to be a dilutional effect.

Analysis of Variance↗
PubMed2001

Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.

We have demonstrated previously that inhibition of angiotensin-converting enzyme (ACE) with enalapril and angiotensin II blockade with losartan improve acetylcholine-dependent endothelial function in resistance vessels of patients with Type II diabetes. It was therefore of interest to examine the effect of losartan on conduit vessel function in this group. The influence of losartan (50 mg daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 12 subjects with Type II diabetes using a randomized, double-blind, placebo-controlled crossover protocol. Conduit vessel endothelial function was assessed using high-resolution ultrasound and the brachial artery response to reactive hyperaemia (flow-mediated dilation; FMD); glyceryl trinitrate (GTN) was used as a non-endothelium-dependent dilator. Losartan administration significantly increased the FMD response from 5.2+/-0.7% (mean+/-S.E.M.) to 7.4+/-0.6% of vessel diameter (P<0.05; paired t-test). There was no effect of losartan on the endothelium-independent responses to GTN (17.8+/-1.8% to 17.6+/-1.2%). Consistent with our previous findings in resistance vessels, administration of 50 mg of losartan daily improves NO-mediated dilation in the conduit vessels of subjects with Type II diabetes. Together with the findings that both ACE inhibition and angiotensin II blockade improve resistance vessel function in this group, it is likely that at least some of the beneficial effect is mediated through the angiotensin II/type I receptor pathway. A type I receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain conduit vessel endothelial function in Type II diabetic subjects.

Angiotensin I↗
PubMed2000

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.

OBJECTIVES: The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function. METHODS: The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography. RESULTS: Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed. CONCLUSIONS: Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.

Angiotensin Receptor Antagonists↗
PubMed2000

Induced hypothermia during emergency department thoracotomy: an animal model.

BACKGROUND: Induced hypothermia is used clinically to prevent ischemic injury during elective procedures. We present an animal model of asanguinous hypothermic (10 degrees C) circulatory arrest, induced through a left anterior lateral thoracotomy after exsanguinating uncontrolled hemorrhage. METHODS: Through a left anterior thoracotomy, 26 swine (45-70 kg) sustained a laceration of the descending thoracic aorta, producing exsanguinating uncontrolled hemorrhage. After 5 minutes of severe hypotension (systolic BP <20 mm Hg), a 22 French Foley catheter was directed cephalad through the enlarged aortic wound. A solution (containing 42.5 mmol/L K+ and precooled to 1 degrees C) was infused to arrest/preserve the heart and brain. A second 24 French Foley catheter was then directed caudally through the same wound. The right atrium was opened to drain the venous system. The animal was cooled with a cardiopulmonary bypass pump (>5L/min) through the Foley catheters. Once 10 degree C was reached, a cannula was placed to the aortic root and the aortic laceration repaired. The animal was maintained at 10 degree C for a total of 90 minutes. Before the rewarming process, the circulation was rinsed with a solution containing normal levels of electrolytes followed by infusion of whole blood. Rewarming was performed by maintaining a 10-degree gradient on the heat exchanger. The first 16 animals were used in nonsurvival experiments to develop the technique and to record dural temperatures and electroencephalogram tracings. The last 10 animals were used to determine long-term survival and neurologic outcome. Group I: seven animals were kept at < 10 degrees C with flows less than 2L/min. Group II: three animals underwent 20, 30, and 40 minutes of no flow once they were cooled to 10 degrees C. After 6 weeks of survival and neurologic examinations, the brains were fixed for histologic evaluations. RESULTS: The average time to cool the head to 18 degrees C and 10 degrees C was 6 minutes and 12 minutes, respectively. The hematocrit fell below 2% by the end of the cooling period. A total of 7 of the 10 animals from the long-term study survived. Group I: five of seven animals survived. Four of the survivors had no appreciable neurologic deficits, were fully functional at 6 weeks, and had no evidence of histologic injury. One of the five survivors in this group had moderate neurologic disability. Of the two animals that died, one died from air embolism from the i.v. line. The second death was in an animal for which maximal cooling to 2.7 degrees C was attempted. Group II: The first two animals that had "no flow" for 20 and 30 minutes were fully functional and had normal neurologic examinations. However, the second animal was found to have brain injury on histologic examination. The last animal in this group died of accidental extubation during recovery. CONCLUSION: Induction of hypothermic arrest through the chest after exsanguination is possible. The further development of this technique may provide an extended state of "suspended animation" to allow for repairs of hemorrhaging injuries in trauma patients who require emergency department thoracotomy.

Animals↗
PubMed1999

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Acetylcholine↗
PubMed1998

CT number distribution and its association with local control and as a marker of lung tumor response to radiation.

An early noninvasive indicator of tumor response to therapy and the ability to predict clinical outcome may potentially enhance disease management. Currently, however, tumor response to therapy is often delayed, potentially compromising disease management. We examined the computed tomography (CT) number or Hounsfield unit distribution to follow lung tumor response to radiation treatment. To help interpret the results, we examined whether the CT number distribution follows a simple two-component model. The CT number distribution was derived from a CT-simulator for 11 patients with lung cancer before and after the initial radiation treatment (1-1.5 months, average 3,407 cGy). Clinical outcomes were followed in 8 patients who received 5,580-6,660 cGy. All patients were scanned serially, using identical radiation imaging parameters (voltage, current, scan time, and slice thickness) in a CT-simulator. The lung tumors were digitally contoured, and software windows were applied to avoid inclusion of lung tissue in the analysis. Histograms and statistical analysis of the CT numbers for the tumor were generated. Radiation-induced CT number or Hounsfield unit (HU) shifts exceeding a threshold (13 HU) in lung tumors were associated with (P=0.04) local control (> or = 10 months). Initial lung tumor size (below 100 cm3) was less well-associated with local control (P=0.26). The change in standard deviation of the CT numbers (derived from the more careful contouring and using software windows) induced by radiation treatment correlated with the change in average CT number (R2=0.71). The change in standard deviation did not correlate with a change in tumor volume (R2=0.02). Radiation treatments reduced the average CT number (P < 0.001). In summary, radiation reduces the CT number and this reduction may be associated with local control at 10 months. A two-component model is consistent with lung tumor number distribution and its response to radiation.

Adult↗
PubMed1997

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.

Administration, Oral↗
PubMed1994

Interaction of fibronectin (FN) cell binding fragments and interleukin-8 (IL-8) in regulating neutrophil chemotaxis.

This study investigated the possible interaction of FN fragments in regulating IL-8-mediated neutrophil chemotaxis in vitro using Neuroprobe microchambers. Human neutrophil suspensions were incubated with purified FN fragments or an RGD-containing peptide and allowed to migrate in response to chemotactically active concentrations of human recombinant IL-8. The 120-kD fragment of FN containing the RGD sequence or an RGD peptide (GRGDSP) inhibited IL-8-mediated neutrophil chemotaxis; however, these RGD peptides did not inhibit neutrophil chemotaxis in response to other chemotactic agents. Furthermore, FN fragments not containing the RGD sequence had no effect on IL-8-mediated chemotaxis. These data suggest that directed migration of neutrophils in response to IL-8 is inhibited in the presence of cell-binding fragments of FN and may represent a local mechanism for terminating neutrophil migration at areas of tissue injury.

Amino Acid Sequence↗
PubMed1986

Risk factors for cardiovascular disease in a diabetic population.

A study of the associations with cardiovascular disease (CVD) was made in subjects attending the Diabetic Clinic at Royal Perth Hospital. The variables examined were sex, age at time of study, age of onset of diabetes, duration of diabetes, mode of treatment, control (as assessed by fasting and post-prandial plasma glucose concentrations and glycosylated hemoglobin concentration), insulin levels in subjects not on insulin, obesity, blood pressure, total- and high-density lipoprotein and triglyceride concentrations, and smoking habit. CVD was diagnosed on the basis of (a) past history of myocardial infarction, (b) definite angina, (c) diagnostic ECG abnormality, and (d) cardiomegaly. A multiple logistic regression model identified the variables showing independent, significant associations with CVD as age, high-density lipoprotein cholesterol, diastolic blood pressure, an interaction between smoking and age and an interaction between treatment mode and blood pressure. As in the population generally, high-density lipoprotein cholesterol is the lipid variable showing the most significant association with prevalence of cardiovascular disease. Smoking is associated with a substantially increased risk of CVD in diabetics up to the age of about 70 yr. The use of oral hypoglycemic agents is associated with a lower prevalence of CVD in normotensive subjects, but with an increased risk in those who have systolic hypertension.

Adult↗
PubMed1984

Clinical macrovascular disease in Caucasoid diabetic subjects: logistic regression analysis of risk variables.

A cross-sectional study of 1084 Caucasoid diabetic subjects in rural Western Australia revealed a high rate of clinical macrovascular disease (46%), including coronary heart disease (13%), stroke (8%), and peripheral vascular disease (38%). Age was the major time-related variable for total macrovascular disease and for peripheral vascular disease, with identical prevalence rates in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes when age was taken into account. In 179 Type 1 diabetic subjects, logistic regression analysis showed no associated risk factors other than age. In 905 Type 2 diabetic subjects the independent risk factors for total macrovascular disease, identified by a forward step-wise selection procedure, were age as the major contributor, with plasma creatinine levels and plasma glucose levels (all p less than 0.001), high-density lipoprotein cholesterol levels, serum total cholesterol levels, and the (supine-erect) systolic blood pressure difference (all p less than 0.05). There were no direct associations with percentage desirable weight, cigarette smoking or male sex. Type 2 diabetic subjects demonstrated a very strong negative association between high-density lipoprotein cholesterol levels and coronary heart disease, and significant associations were found also between plasma glucose levels and coronary heart disease (p less than 0.01), and glycosylated haemoglobin levels and peripheral vascular disease (p less than 0.001).

Adolescent↗
PubMed1982

Cholesterol and lipoprotein-cholesterol levels in Western Australian rural diabetics.

Total cholesterol, high-density lipoprotein-cholesterol (HDL-C) and non-HDL-cholesterol (non-HDL-C) were measured in the serum of diabetics from four country regions in Western Australia in order to document the levels and to examine the relationships between treatment mode, degree of diabetic control and lipid concentrations. In most age groups total cholesterol and non-HCL-C did not differ from levels in a large reference population, but HDL-C levels were generally lower. Male NIDDM patients on insulin had greater HDL-C levels than patients on oral hypoglycaemics, but their degree of control as determined by the level of glycosylated haemoglobin was poorer, and amongst female patients on insulin those with higher HDL-C levels had poorer control. These results confirm previous reports of higher HDL-C levels in patients on insulin, but are contrary to reports suggesting that better control is associated with higher HDL-C levels.

Adult↗
PubMed1981

Congenital coronary aneurysms nine years following saphenous vein bypass graft surgery.

A 34-year-old woman with two congenital coronary aneurysms received a saphenous vein bypass graft (SVBG) as treatment for a thrombosed right coronary artery aneurysm 9 years ago. The angiographic and surgical findings were reported at that time [1]. In 1979, she received a sequential SVBG to the left anterior descending and first diagonal coronary arteries following recurrence of angina and progressive occlusion of the left coronary artery aneurysm. She is believed to have the longest angiographically documented course following operation, and her case history is reported to aid in establishing the natural history of this unusual condition and its surgical management.

Adult↗