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Biomedical subjects

Jill J F Belch

Publications and source records attributed to Jill J F Belch.

At least 19 recordsLinked to original sources
PubMed2007

Left ventricular hypertrophy is present in one-half of newly-diagnosed peripheral arterial disease patients.

OBJECTIVES: Peripheral arterial disease (PAD) patients are at high risk of cardiac death. Coincidental but silent coronary disease is obviously a major contributor but left ventricular hypertrophy (LVH) could be a second major contributor. METHODS: To investigate whether LVH could really be making a large contribution to cardiac death in PAD, we assessed the prevalence of LVH when PAD was first diagnosed. RESULTS: The prevalence of echo LVH when left ventricular mass was indexed to body surface area was 50%. Although office blood pressure and 24-h blood pressure were both significantly higher in those with LVH, in clinical practice, a contemporaneous blood pressure measurement (office or 24 h) at the time of PAD diagnosis would only partially identify those with LVH. For example, an office blood pressure cut-off of < 140/90 mmHg was found in 27% of all LVH cases and a 24-h blood pressure cut-off of < 125/80 mmHg was found in 24% of all LVH cases. CONCLUSION: In conclusion, there is already a high prevalence of LVH in patients at first diagnosis of PAD. LVH is therefore common enough in PAD patients to potentially make a major contribution to cardiac death, which means that future research should now investigate whether screening for and regressing LVH when present would actually reduce cardiac deaths over and above merely achieving target blood pressure.

Aged↗
PubMed2006

Is chronic fatigue syndrome associated with platelet activation?

Chronic fatigue syndrome (CFS) is a debilitating condition that has no known aetiology or pathophysiology. Recent investigations by other workers have suggested that individuals with CFS may have a hypercoagulable state. This study investigated various aspects of platelet activation and function in 17 patients with CFS and in 16 age-matched and sex-matched healthy controls. Platelet aggregation, platelet volume and coagulation tests were performed. Platelet aggregation was investigated by means of the photometric changes using citrated platelet-rich plasma, whole blood aggregation was calculated as the percentage fall in single platelet counts and the coagulation tests were performed on an automatic microcentrifugal analyser.A trend was observed for the patients to have lower aggregation results and a reduced mean platelet volume. However, this only reached statistical significance for one result; the rate of the aggregation slope by 1.0 microg/ml collagen [CFS patients, 18 (9-28) versus controls, 32.5 (19-36); Mann-Whitney U test, P = 0.029]. No significant differences were found for any of the measurements of coagulation. These results are in contrast to previously reported findings. However, due to the heterogeneous nature of the disease, and the resulting lifestyles of the patients, caution should be taken when comparing one group of patients with another. Nevertheless, we certainly found no evidence of increased platelet activation or of a hypercoagulable state in patients with CFS and, on the basis of these results, anti-platelet or anti-coagulant therapy is not warranted.

Adult↗
PubMed2005

Changes in endothelial function precede the clinical disease in women in whom preeclampsia develops.

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (P<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (P<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (P<0.05 and P<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (P<0.05 and P<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.

Acetylcholine↗
PubMed2005

Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms.

The aetiology of chronic fatigue syndrome (CFS) is unknown; however, recent evidence suggests excessive free radical (FR) generation may be involved. This study investigated for the first time levels of 8-iso-prostaglandin-F(2 alpha)-isoprostanes alongside other plasma markers of oxidative stress in CFS patients and control subjects. Forty-seven patients (18 males, 29 females, mean age 48 [19--63] years) who fulfilled the Centres for Disease Control classification for CFS and 34 healthy volunteers (13 males, 21 females, 46 [19--63] years) were enrolled in the study. The CFS patients were divided into two groups; one group had previously defined cardiovascular (CV) risk factors of obesity and hypertension (group 1) and the second were normotensive and nonobese (group 2). Patients had significantly increased levels of isoprostanes (group 1, P=0.007; group 2, P=0.03, unpaired t test compared to controls) and oxidised low-density lipoproteins (group 2, P=0.02) indicative of a FR attack on lipids. CFS patients also had significantly lower high-density lipoproteins (group 1, P=0.011; group 2, P=0.005). CFS symptoms correlated with isoprostane levels, but only in group 2 low CV risk CFS patients (isoprostanes correlated with; total symptom score P=0.005; joint pain P=0.002; postexertional malaise P=0.027, Pearson). This is the first time that raised levels of the gold standard measure of in vivo oxidative stress (isoprostanes) and their association with CFS symptoms have been reported.

Adult↗
PubMed2004

Spiral laminar flow in the abdominal aorta: a predictor of renal impairment deterioration in patients with renal artery stenosis?

BACKGROUND: Spiral or helical arterial blood flow patterns have been widely observed in both animals and humans. The absence of spiral flow has been associated with carotid arterial disease. The aim of this study was to detect the presence of aortic spiral flow using magnetic resonance imaging (MRI) and to evaluate the relationship of the presence of spiral aortic flow with renal arterial disease and renal function in the follow-up of patients with suspected renal atheromatous disease. METHODS: Prospective study of 100 patients with suspected renal arterial disease and 44 patient controls. Using a 1.5 T MRI unit (Siemens Symphony), phase contrast flow quantification and three-dimensional contrast enhanced MR angiography of the abdominal aorta were performed. Renal arterial stenoses (RAS) were classified minimal, moderate or severe. Renal function was followed at 3 months before and 6 months after MRI. RESULTS: Non-spiral flow was more prevalent in patients with more severe RAS. Renal impairment progressed significantly in severe RAS without spiral flow (P = 0.0065), but did not progress significantly in severe RAS with spiral flow (P = 0.12). In minimal or moderate RAS with or without spiral flow there was no significant progression (P = 0.16, 0.13, 0.47, 0.092, respectively). CONCLUSIONS: Aortic spiral blood flow can be assessed with MRI. Lack of aortic spiral blood flow in patients with severe RAS is associated with significant short-term renal function deterioration. Determination of blood flow patterns may be a useful indicator of renal impairment progression in patients with suspected renal artery stenosis.

Adult↗
PubMed2004

Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans.

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

Acetylcholine↗
PubMed2004

The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria.

PURPOSE: The Centers for Disease Control (CDC)-1994 definition of chronic fatigue syndrome (CFS) is very broad, and there have been suggestions that it lacks specificity. To test this, we have compared three groups of patients, all of whom fulfill the criteria but self-report different etiologies. METHODS: Patients with self-reported symptoms which developed sporadically (sCFS, n=48); after Gulf War service (GW, n=24); and following exposure to organophosphate insecticides (OP, n=25) underwent a clinical examination, completed the MOS SF-36 quality of life and Hospital Anxiety and Depression scales, and were assessed for major and minor criteria for CDC-1994 CFS. RESULTS: Significant differences in simple clinical measures and outcome measures were observed between groups. The GW group had significantly more severe physical symptoms-fatigue, muscle and multi-joint pain-than OP or sCFS, and the sCFS group was significantly less impaired than the other two groups in terms of role emotional and mental health. In all three groups, a majority of patients exhibited muscle weakness in the lower limbs, and significant numbers of patients had absent or abnormal reflexes. CONCLUSIONS: Differences in simple, easily performed clinical outcome measurements can be observed between groups of patients, all of whom fulfill the CDC-1994 criteria for CFS. It is likely that their response to treatment may also vary. The specificity of the CFS case definition should be improved to define more homogeneous groups of patients for the purposes of treatment and research.

Adult↗
PubMed2004

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure.

In the present study, we have investigated whether the peripheral cholinergic abnormalities that we have reported previously [Spence, Khan and Belch (2000) Am. J. Med. 108, 736-739] in patients with chronic fatigue syndrome (CFS) are also present in those with Gulf War syndrome (GWS) and agricultural workers exposed to organophosphate pesticides, where cholinesterase inhibition is specifically implicated. We also looked at whether these abnormalities might be due to a reduction in the activity of cholinesterase expressed on the vascular endothelium. We used laser Doppler imaging to measure the forearm skin blood flow responses to iontophoresis of acetylcholine and of methacholine (which is resistant to breakdown by cholinesterase) in patients with CFS, GWS and those with a history of ill health after definite organophosphate exposure, as well as in matched healthy controls. The response to acetylcholine was significantly higher in patients with CFS than in controls ( P =0.029, repeated-measures ANOVA), but was normal in those with GWS and those exposed to organophosphates. The methacholine response was higher than the acetylcholine response in all patient groups except for those with CFS, where there was no difference between the responses. Although there are many clinical similarities between these three illnesses, our results indicate peripheral cholinergic abnormalities in the vascular endothelium of only patients with CFS, suggesting that this syndrome has a different aetiology, which might involve inhibition of vascular cholinesterase.

Acetylcholine↗
PubMed2004

Dietary lipids and vascular function: UK Food Standards Agency workshop report.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating the effect of dietary lipids on vascular function. The workshop highlighted the need for intervention studies to be sufficiently powered for these measures and that they should be corroborated with other, more validated, risk factors for CVD. Work presented at the workshop suggested a beneficial effect of long-chain n-3 PUFA and a detrimental effect of trans fatty acids. The workshop also considered the importance of the choice of study population in dietary intervention studies and that "at risk" subgroups within the general population may be more appropriate than subjects that are unrepresentatively healthy.

Cardiovascular Diseases↗
PubMed2003

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects.

OBJECTIVE: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. METHODS: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. RESULTS: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation (P=0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. CONCLUSIONS: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2-3 times/week) might have significant beneficial effects on cardiovascular function and health.

Acetylcholine↗
PubMed2003

Impaired microvascular function in normal children: effects of adiposity and poor glucose handling.

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat (r = -0.20, P < 0.05 and r = -0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l-1) showed significantly lower vasodilatation to both ACh (P < 0.005) and SNP (P < 0.02) than those in the lower quintile (range 3.9-4.9 mmol l-1). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile (P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin (r = 0.59, P < 0.001) and with the fasting insulin resistance index (r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated (r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.

Acetylcholine↗
PubMed2003

Two-dimensional flow quantitative MRI of aortic arch blood flow patterns: Effect of age, sex, and presence of carotid atheromatous disease on prevalence of spiral blood flow.

PURPOSE: To determine the effect of age, sex, and presence of carotid atheromatous disease on the presence of aortic spiral blood flow pattern using two-dimensional flow quantitative magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixty subjects (37 women, 23 men) were examined. Prospective phase contrast flow quantitative MRI (1.5 T, Siemens Symphony) sequences in the plane of the aortic arch, and three-dimensional contrast-enhanced MR angiography of the vessels from the aortic arch to the circle of Willis, were performed. Flow quantitative analysis, using circular regions of interest, in the root, apex, and descending aortic arch to determine the presence of a spiral blood flow pattern was undertaken. The results were correlated with the subjects age, sex, and presence of significant carotid arterial disease. RESULTS: A spiral blood flow pattern was seen during diastole in 43 of 50 (86%), 42 of 48 (88%), and in 26 of 28 (93%) subjects in the root, apex, and descending aortic arch, respectively. Spiral flow was seen during systole in 14 of 35 (40%), 20 of 47 (42%), and 11 of 31 (35%) subjects in the root, apex, and descending aortic arch, respectively. There was no clear effect of age or sex on the presence of spiral flow. Carotid disease was associated with a significant reduction in the prevalence of systolic spiral flow from 51%-19% subjects (P < 0.05). CONCLUSION: Spiral flow pattern can be seen in the arch of the aorta in clinical practice using flow quantitative MRI. The prevalence of spiral flow pattern does not appear affected by subject age or sex. Carotid atheromatous disease is associated with a reduction in prevalence of systolic spiral flow pattern in the aortic arch.

Adolescent↗
PubMed2003

Chemical synthesis and microvascular effects of new nitric oxide donors in humans.

Nitric oxide (NO) is produced continuously from the endothelium and plays a pivotal role in the control of vascular tone. Many of the current therapeutic agents that increase blood flow through production of NO have to be taken orally and can produce significant adverse side effects. We now report on some novel NO-donor drugs, based on thiosugars that generate NO spontaneously. From the range of compounds synthesized, D-SNAG ( S -nitroso-1-thio-2,3,4,6-tetra- O -acetyl-beta-D-glucopyranose) was as effective a vasodilator as any other and, as it was the easiest to synthesize, we undertook a more detailed evaluation to understand the chemistry and mode of action of its vasodilator effect. From the chemical kinetic data, we found that NO release occurred predominantly by thermal decomposition, with a 20-fold increase in decomposition rate between 19 and 37 degrees C. In the forearm of eight normal male subjects, we found that D-SNAG produced a significant dose-dependent vasodilator effect ( P =0.001) with good reproducibility (19%) on repeated testing. We propose that delivery of NO from D-SNAG to the forearm skin microvessels most probably occurs by diffusion across the epidermis. Since such compounds release NO in a non-enzymic manner following topical application, they might produce an attractive therapeutic source of localized NO delivery without inducing systemic side effects.

Adult↗
PubMed2003

Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome.

Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism. Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. To investigate this further, we studied the time course of ACh-induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age- and gender-matched healthy control subjects. No differences in peak blood flow was seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13.7 +/- 11.3 versus 8.9 +/- 3.7 min (P = 0.03), respectively, and time taken to decay to 50% of the peak response was 24.5 +/- 18.8 versus 15.1 +/- 8.9 min (P = 0.03), respectively. Prolongation of ACh-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

Acetylcholine↗
PubMed2003

Dark chocolate inhibits platelet aggregation in healthy volunteers.

Cardiovascular disease is a leading cause of death in the UK. The flavonoids found in cocoa may produce a cardio-protective role for chocolate with a high cocoa content. Thirty healthy volunteers were randomised to receive 100 g of white, milk or dark chocolate, and assessments of platelet function were undertaken on venous blood samples before and after chocolate consumption. White and milk chocolate had no significant effect on platelets. However dark chocolate inhibited collagen-induced platelet aggregation in platelet rich plasma. In the future dark chocolate may have a role in prevention of cardiovascular and thromboembolic diseases.

Blood Platelets↗