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Biomedical subjects

J J Belch

Publications and source records attributed to J J Belch.

At least 19 recordsLinked to original sources

Differences in endothelial function and vascular reactivity between Scottish and Arabic populations.

BACKGROUND: The endothelium is a major organ that plays a central role in the regulation of blood flow, resists thrombus formation and maintains blood fluidity. Environmental, dietary, but also genetic factors might affect endothelial cell function and vascular activity. METHODS AND RESULTS: Endothelium-dependent and -independent vascular responses were evaluated in 42 male subjects from two different populations: 30 Scottish and 12 Arabic (transient visitors to UK) (20-41 years old). Endothelium-dependent and -independent vascular responses were measured in the forearm skin using laser Doppler imaging after iontophoresis of increasing doses of acetylcholine and sodium nitroprusside, respectively. Endothelium-dependent responses were significantly greater in Arabic subjects compared with responses in Scottish subjects (mean ACh ratio 4.9 +/- 1.2 v 3.8 +/- 1.5, respectively, P = 0.013, ANOVA). Although there was no significant difference between the groups in endothelium-independent vascular responses (mean SNP ratio 3.4 +/- 1.2 v 2.8 +/- 1.2, respectively, P = 0.26, ANOVA), there was a trend however towards a higher peak SNP response in the Arabic group (5.3 +/- 1.5 v 4.1 +/- 1.9, respectively, P = 0.019). CONCLUSIONS: These results suggest that a significant difference exists in the endothelial function and vascular reactivity between these populations. Although the reasons for these differences are not clear, they may be related to differences in life styles, tradition, food intake, environmental and genetic factors.

Acetylcholine↗

Investigation of cutaneous microvascular activity and flare response in patients with fibromyalgia syndrome.

OBJECTIVES: To assess microvascular activity in the skin of patients with fibromyalgia syndrome (FMS) as compared with normal controls. METHODS: Fifteen patients, who fulfilled the American College of Rheumatology criteria for FMS, and 15 age- and sex-matched healthy controls, were studied. The microvascular activity of the skin overlying the trapezius muscle was quantified using iontophoresis of acetylcholine as an endothelial-dependent vasodilator and sodium nitroprusside as an endothelial-independent vasodilator. We also studied the flare response by iontophoresing acetylcholine continuously for 10 min to stimulate a ring of nociceptor c-fibre endings in the skin. RESULTS: There was no significant difference in cutaneous vascular responses to short-duration iontophoresis of acetylcholine and sodium nitroprusside at the three different doses used. The area under the curve (AUC) (mean+/-s.e.m.) for acetylcholine baseline, 20, 40, and 80 s were 6+/-0.7, 23+/-6, 45+/-7 and 66+/-10 AU for patients and 11+/-4, 24+/-3, 49+/-7 and 62+/-12 AU for controls, respectively (P=0.2, 0.9, 0.7, 0.8, respectively). The corresponding figures for sodium nitroprusside were 5+/-1, 18+/-7, 51+/-14 and 68+/-14 AU for patients and 8+/-3, 13+/-2, 39+/-5 and 61+/-9 AU for controls, respectively (P=0.2, 0.5, 0.4, 0.7, respectively). There was also no significant difference in the flare response in patients with FMS as compared with control subjects (119+/-15 and 131+/-13 AU, respectively; P=0.57). CONCLUSION: There are no significant differences in cutaneous microvascular reactivity between patients with FMS and control subjects.

Acetylcholine↗

The Scottish Heart and Arterial Risk Prevention (SHARP) survey of cardiovascular risk: regional differences.

The objective was to explore variation in cardiovascular risk profiles within the Scottish workforce over different regions of Scotland by a planned review of survey data of workplaces throughout Scotland, surveyed between December 1991 and March 1996. The subjects sampled were 19,400 men and women aged between 18 and 70, who were in work and apparently healthy at the time of screening. The results showed that the regions of Scotland may be distinguished through particular risk factors and also by using a single summary score (the SHARP risk score). Overall the Perth and Kinross region tops the league for cardiovascular risk (with the main contributing factors being smoking and high blood pressure); regions of least risk are Inverness-shire and Edinburgh. There are statistically significant differences to be discerned in the regional distribution of cardiovascular risk within the working population of Scotland.

Cardiovascular Diseases↗

Biochemical and biophysical markers of endothelial dysfunction in adults with hypopituitarism and severe GH deficiency.

Adult hypopituitarism is known to be associated with reduced life expectancy related to excess vascular events, and endothelial dysfunction is present in patients with this condition. We studied the relationship between biophysical and biochemical markers of endothelial dysfunction, including E-selectin, intercellular cell adhesion molecule-1, von Willebrand factor, and thrombomodulin in 52 adult patients with hypopituitarism and severe GH deficiency (<2 ng/ml on provocative testing) compared with 54 age-, sex-, and smoking-matched normal controls. We also examined endothelium-dependent dilatation of the brachial artery to postischemic occlusion and carotid artery morphology (intima-media thickness) by high-resolution ultrasonography. The patients were stable on conventional hormone replacement therapy but not on GH therapy, and none of the subjects had a known risk factor for vascular disease. Levels of E-selectin [57 +/- 3 vs. 49 +/- 2 ng/ml (mean +/- SEM)] (P < 0.043), intercellular cell adhesion molecule-1 (308 +/- 11 vs. 266 +/- 10 ng/ml) (P < 0.001), thrombomodulin (49 +/- 3 vs. 35 +/- 2 ng/ml) (P < 0.001), and von Willebrand factor (132 +/- 7% vs. 105 +/- 5%) (P < 0.004) were significantly higher in patients than in controls. Brachial artery endothelium-dependent dilatation was significantly lower in patients than in controls [4.7% (0.00-9.77) vs. 10.5% (6.4-16.2) (median, interquartile range)] (P < 0.001). This difference in endothelium-dependent dilatation was more marked in female patients than in controls (P < 0.003), although it disappeared when estrogen-sufficient female patients were compared with controls (P = 0.31). However, the female patients who were not replaced with estrogen continued to show a striking difference compared with estrogen-deficient control females (P < 0.004). There was no difference in carotid intima-media thickness between patients of either sex and controls. On univariate analysis, brachial artery endothelium-dependent dilatation correlated inversely with intercellular cell adhesion molecule-1 (r = -0.225, P < 0.033). Intercellular cell adhesion molecule-1 correlated positively with E-selectin (r = 0.466, P < 0.0001) and negatively with IGF-I (r = -0.238, P < 0.016). E-selectin correlated with thrombomodulin (r = 0.215, P < 0.034) and von Willebrand factor (r = 0.218, P < 0.03) and negatively with IGF-I (r = -0.255, P < 009). Thrombomodulin correlated positively with von Willebrand factor (r = 0.422, P < 0.0001) and inversely with IGF-I (r = -0.266, P < 0.008). These correlations persisted after correction for age, sex, body mass index, and waist to hip ratio, with the exception of IGF-I, which now correlated with thrombomodulin only. These results confirm significant endothelial dysfunction in hypopituitarism and provide insight into the relationship of biochemical and biophysical markers of early atherosclerosis in hypopituitary GH-deficient adults. The negative correlation of IGF-I with some biochemical markers of endothelial dysfunction and the predictive nature of GH deficiency in stepwise regression analysis in this study supports the hypothesis that GH deficiency may play a role in these abnormalities. Future studies will determine whether GH treatment can reverse these abnormalities. Furthermore, the more significant endothelium-dependent dilatation abnormality in the female estrogen-deficient subjects compared with those who were estrogen replete suggests that estrogen replacement in these patients is a crucial element in protecting against vascular disease.

Adult↗

Antiplatelet and anticoagulant therapy to prevent bypass graft thrombosis in patients with lower extremity arterial occlusive disease.

The incidence of graft failure for above knee femoropopliteal grafts is described by the European Consensus Document on Critical Limb Ischaemia. It occurs in approximately 15% of patients when vein is used for the grafting procedure and in 20% of patients when PTFA (polytetrafluoroethylene) or other prosthetic material is used. Femorodistal grafts have a much poorer outcome with 45% and 75% failure rates for vein and prosthetic grafts, respectively. Prevention of primary graft failure and thus the need for surgical reintervention is of major clinical and economic importance. Early failure, occurring within one month of operation, is usually due to technical error such as poor patient selection or operative technique. Approximately 10% of graft failures will fall into this time period. When grafts thrombose after two years, progression of native atherosclerosis either proximally or distally is the usual cause. This accounts for 2-3% of all graft failures each year. The most common time for grafts to fail is between one month and two years (80% of all failures) and this is the same period in which graft stenoses are now known to develop. There are few evidence-based recommendations for the use of pharmacological agents in maintaining graft patency following peripheral vascular surgery. This article reviews the evidence for or against the use of anticoagulant and antiplatelet therapy for the prevention of bypass graft thrombosis in patients with peripheral arterial occlusive disease.

Anticoagulants↗

[Free radical scavenging activity of sulfonylureas: a clinical assessment of the effectiveness of gliclazide].

In long-term clinical studies the beneficial effects of gliclazide on platelets have been related to a reduction in oxidative stress. This property is because of gliclazide's free radical scavenging ability that relates to the unique amino azabicyclo-octane ring, which is grafted on to the sulfonylurea. During a blinded clinical trial, the possible effects of gliclazide were assessed in 30 non-insulin-dependent diabetic patients. All patients had been treated for diabetes for more than 2 years (mean 8 years) and had been established on glibenclamide for over 2 years with or without adjunctive metformin therapy. Patients were studied for 6 months and randomized to continue either their present dose of glibenclamide or to be converted to an equipotent dose of gliclazide. Measurements were taken of hemostatic variables, the oxidative status of the plasma, and the redox status, both extracellularly as plasma albuminthiols (PSH) and lipid peroxides, and intracellularly as red blood cell superoxide dismutase activity (SOD). At 3 months, diabetic control was unaltered, but there were significant improvements in the oxidative status of the gliclazide-treated patients. Lipid peroxides decreased (8.3 +/- 1.1 to 7.0 +/- 0.06 mumol/l, P < 0.01) and red blood cell SOD increased (135 +/- 21 to 152 +/- 36 micrograms/ml, P < 0.05). PSH levels were unaltered at 453 +/- 38 mumol/l, whereas they had decreased significantly in the glibenclamide patients (414 +/- 34 mumol/l, P < 0.05), resulting in a significant difference between the 2 treatment groups (P < 0.004). Platelet reactivity to collagen also improved in the gliclazide-treated patients, decreasing from 65.1% +/- 14% to 50.8 +/- 24% (p < 0.01). The reactivity of the platelets remained unaltered in the glibenclamide patients. At 6 months, the significant differences between the 2 treatment groups remained. Hence, gliclazide was shown in a clinical study to have free radical scavenging activity independent of glycemic control.

Adult↗

Assessment of microvascular endothelial function in human skin.

Endothelial dysfunction is an important factor in many cardiovascular diseases, and is commonly associated with impaired endothelium-mediated vasodilatation. Information about the mechanisms behind this dysfunction has come largely from animal studies or, in humans, through invasive techniques that are not specific to one vascular bed. We have developed protocols to assess endothelial function non-invasively in the cutaneous microcirculation by measuring blood flow responses to four receptor-specific vasoactive compounds. Cumulative doses of acetylcholine, methacholine, bradykinin and substance P were administered iontophoretically to the forearm skin of healthy volunteers on two to three occasions. Dose-dependent increases in skin microvascular blood flow in response to these drugs were measured with laser Doppler imaging. Vascular responses to acetylcholine and methacholine were reasonably consistent, with coefficients of variation of approx. 17%. The coefficients of variation for bradykinin and substance P were much poorer, as high as 70% for some doses. This might partly be a consequence of the more unpredictable effects of histamine release in the vasoactive behaviour of these two agonists. Although it might be advantageous to find other agonists with which to test the function of different receptor pathways, we have shown that just acetylcholine and methacholine can currently be used with iontophoresis to allow sensitive and reproducible assessment of endothelial function.

Acetylcholine↗

Free radical scavenging activity of sulfonylureas: a clinical assessment of the effect of gliclazide.

In long-term clinical studies the beneficial effects of gliclazide on platelets have been related to a reduction in oxidative stress. This property is because of gliclazide's free radical scavenging ability that relates to the unique amino azabicyclo-octare ring, which is grafted on to the sulfonylurea. During a blinded clinical trial, the possible effects of gliclazide were assessed in 30 non-insulin-dependent diabetic patients. All patients had been treated for diabetes for more than 2 years (mean 8 years) and had been established on glibenclamide for over 2 years with or without adjunctive metformin therapy. Patients were studied for 6 months and randomized to continue either their present dose of glibenclamide or to be converted to an equipotent dose of gliclazide. Measurements were taken of hemostatic variables, the oxidative status of the plasma, and the redox status, both extracellularly as plasma albumin-thiols (PSH) and lipid peroxides, and intracellularly as red blood cell superoxide dismutase activity (SOD). At 3 months, diabetic control was unaltered, but there were significant improvements in the oxidative status of the gliclazide-treated patients. Lipid peroxides decreased (8.3 +/- 1.1 to 7.0 +/- .06 micromol/L, P < .01) and red blood cell SOD increased (135 +/- 21 to 152 +/- 36 microg/mL, P < .05). PSH levels were unaltered at 458 +/- 38 micromol/L, whereas they had decreased significantly in the glibenclamide patients (414 +/- 34 micromol/L, P < .05), resulting in a significant difference between the 2 treatment groups (P < .004). Platelet reactivity to collagen also improved in the gliclazide-treated patients, decreasing from 65.1% +/- 14% to 50.8% +/- 24% (P < .01). The reactivity of the platelets remained unaltered in the glibenclamide patients. At 6 months, the significant differences between the 2 treatment groups remained. Hence, gliclazide was shown in a clinical study to have free radical scavenging activity independent of glycemic control.

Adult↗

Mean platelet volume is a useful parameter: a reproducible routine method using a modified Coulter thrombocytometer.

The principal physiological function of platelets is to promote haemostasis but they also contribute to thrombosis and atherogenesis. Platelet volume is a marker and possibly a determinant of platelet function in that large platelets are more active than normal sized platelets. Mean platelet volume (MPV), a measure of platelet size, reflects changes in either the level of platelet stimulation or the rate of platelet production. For these reasons, we have developed a sensitive instrument to measure platelet volume, which we believe is more reliable and specific than previously used instruments. It is based on a computer-interfaced Coulter Thrombocytometer and a pulse analyser including a high-speed baseline restorer. We have developed a reproducible method to assay MPV and from the histogram derived the median (MED) and the skewness (SK) values. We have looked at the effects of anticoagulant used and time elapse prior to assay. A normal range has been established for MPV which correlates directly with MED and inversely with SK. The MPV decreases with age but there is no difference between genders. We have demonstrated a negative correlation between whole blood platelet number and MPV and MED, and a direct relationship with the SK of the histogram of the platelet volume.

Adolescent↗

Evening primrose oil and borage oil in rheumatologic conditions.

Diets rich in arachidonic acid (20:4n-6) lead to the formation of 2-series prostaglandins (PGs) and 4-series leukotrienes (LTs), with proinflammatory effects. Nonsteroidal antiinflammatory drugs are used in rheumatoid arthritis to inhibit cyclooxygenase (prostaglandin-endoperoxide synthase), thereby decreasing production of 2-series PGs. Lipoxygenase activity remains intact, however, allowing LT production (eg, synthesis of LTB(4), a potent inflammatory mediator) to continue. Altering the essential fatty acid (EFA) content of the diet can modify some of these effects. Ingestion of a diet rich in evening primrose oil elevates concentrations of dihomo-gamma-linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE(1). DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and thus suppress inflammation. The results of in vitro and animal work evaluating EFAs in inflammatory situations are encouraging, which has stimulated clinical workers to evaluate these compounds in rheumatoid arthritis. Several well-controlled, randomized clinical studies have now been completed in which various EFAs were evaluated as treatments. The results of most of these studies suggest some clinical benefit to these treatments; these data are reviewed here.

Anti-Inflammatory Agents, Non-Steroidal↗

Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension.

Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses (eg, vitamins C and E). A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase. We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age. We examined 23 subjects (11 patients with type 2 diabetes and 12 healthy age-matched control subjects) in 2 parallel groups. The subjects were administered 300 mg allopurinol in a randomized, placebo-controlled study in which both therapies were administered for 1 month. Endothelial function was assessed with bilateral venous occlusion plethysmography, in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured. Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30% (3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1). min(-1) allopurinol versus placebo; P=0.012, 95% CI 0.14, 1.30) but did not affect the nitroprusside response in patients with type 2 diabetes. There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects. Allopurinol improved endothelial function to near-normal levels. Regarding markers of free radical activity, the level of malondialdehyde was significantly reduced (0.30+/-0.04 versus 0. 34+/-0.05 micromol/L for allopurinol versus placebo, P=0.03) in patients with type 2 diabetes but not in control subjects. The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects. In the former group, allopurinol restored endothelial function to near-normal levels.

Age Factors↗

Results of a survey of cardiovascular risk factor prevalence amongst health care workers. The Executive Committee of SHARP--(Scottish Heart and Arterial Risk Prevention).

Summary analyses of screening data were used to ascertain the cardiovascular risk profile in a sample of health care workers in Scotland. A sample of NHS staff (298 women and 78 men) were screened during visits to Perth Royal Infirmary (PRI) in 1996 and 1997. Comparisons were made within subsets and with previous screening studies. Health care workers have been a neglected component of the workforce for receiving education about risk factors. The high prevalence of smokers found in this sample should be a cause for concern.

Adult↗

Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes.

OBJECTIVE: Vascular disease in type 1 diabetes is a complex and multifactorial process, which probably begins in childhood in association with the onset of diabetes. To determine the possible factors involved, we measured microvascular responses to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators in 56 patients with type 1 diabetes (aged 9-22 years) and 22 control subjects. RESEARCH DESIGN AND METHODS: Skin perfusion was measured at the dorsum of the foot using laser Doppler flowmetry during low-current iontophoresis of acetylcholine and sodium nitroprusside. Maximum vasodilator function was measured during local 44 degrees C skin heating. RESULTS: Vascular responses were significantly reduced in patients with type 1 diabetes compared with responses in control subjects: acetylcholine (P<0.01, analysis of variance [ANOVA]), sodium nitroprusside (P<0.01, ANOVA), and local heating (P<0.02. Mann-Whitney U test). Endothelium-dependent responses were related to duration of diabetes (r = -0.38, P<0.01) and to glycemic control (r = 0.37, P<0.01). Significant correlations were found in the patient group between responses to acetylcholine and sodium nitroprusside (r = 0.28, P<0.05) but not to heating, suggesting that a common factor (e.g., nitric oxide activity) may be responsible for the abnormal vascular responses to these chemicals. CONCLUSIONS: Early changes in microvascular function are present in young patients with type 1 diabetes, long before the initial clinical presentation. These abnormalities may be related to complex interactions between structural abnormalities and functional changes in the endothelium, smooth muscle, and nitric oxide activity.

Acetylcholine↗

Elevated levels of soluble E-selectin in diabetic patients with severe symptomatic peripheral arterial occlusive disease requiring angioplasty. A possible role in diabetic vascular disease?

BACKGROUND: To study levels of E-selectin in patients with peripheral arterial occlusive disease who were undergoing percutaneous transluminal angioplasty. METHODS: Experimental design and setting: Cross sectional case control study, conducted in a teaching hospital. SUBJECTS: Seven patients with type-2 (non-insulin dependent) diabetes mellitus undergoing transluminal angioplasty for symptomatic peripheral arterial occlusive disease, had blood tests for sE-selectin measurement, and were compared to a similar groups of age and sex matched non-diabetic patients with arteriopathy who are undergoing the same procedure. Also evaluated were a group of diabetic patients and healthy non-diabetics with no peripheral arterial disease. RESULTS: The levels of sE-selectin in the two diabetic groups were significantly higher than the non-diabetic groups measuring at 77 ng/ml (53-120) and 79 ng/ml (43-98) (median, range) vs 54 ng/ml (24-104) in the non-diabetic with arteriopathy, and 42 ng/ml (35-66) in the normal healthy controls, p<0.04, p<0.003 respectively, Mann Whitney "U" test. CONCLUSIONS: We have demonstrated significantly high values of soluble E-selectin in patients with diabetes mellitus requiring angioplasty for symptomatic peripheral arterial occlusive disease. This suggests that sE-selectin may be involved in the diabetic angiopathic process. It may act as a precursor for smooth muscle proliferation.

Angioplasty, Balloon↗

Seasonal variation in plasma levels of endothelin-1 and nitric oxide.

BACKGROUND: There is a seasonal variation in the incidence of stroke and coronary heart disease with admissions to hospital being higher in the colder months of the year. The mechanism whereby this winter prevalence of vascular disease occurs is still not fully understood. The aim of our study was to measure plasma levels of vasoactive compounds throughout the year to establish whether or not there were any fluctuations which could play a part in the higher winter incidence. METHODS: We measured plasma levels of the vasoconstrictive endothelin-1 (ET) and the vasorelaxant nitric oxide (NO) throughout the year. Blood samples were collected from 176 normal individuals. Samples were collected between 8.00 and 10.00 hours after an overnight fast of at least 12 hours. RESULTS: Results were divided into two-monthly intervals and analysed using a Kruskal-Wallis one-way analysis of variance and Mann-Whitney U tests (SPSS). We found a significant seasonal variation in both parameters. Mean levels of endothelin were highest in January/February (4.0 pg/ml) and lowest in May/June (2.3 pg/ml), whereas plasma 5 nitric oxide levels were lowest in January/February (5.7 microM) and highest in September/October (9.9 microM); p values were <0.0001 (Jan/Feb vs May/June) and 0.049 (Jan/Feb vs Sept/Oct), respectively. CONCLUSIONS: The high levels of the vasoconstrictor endothelin combined with low levels of vasorelaxant nitric oxide may account in part for the increased incidence of stroke and coronary heart disease seen in these months.

Aged↗

Endothelial activation and response in patients with hand arm vibration syndrome.

BACKGROUND: Hand-arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide. METHODS: Blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the inflammatory cytokine interleukin 8 (IL-8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects. RESULTS: sICAM-1 levels were statistically higher (P = 0.02, Mann-Whitney U-test) and IL-8 levels (P < 0.01, Mann-Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05, ANOVA). CONCLUSIONS: In this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM-1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL-8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.

Acetylcholine↗

Skin perfusion in patients with erythromelalgia.

BACKGROUND: Erythromelalgia (EM) is a chronic disorder characterized by intermittent pain, warmth and erythema of the extremities. Symptoms can be precipitated by increasing the temperature of the affected limb and can be partially relieved by direct cooling. MATERIALS AND METHODS: Microvascular assessment was conducted under 'hot' (28 degrees C) environmental conditions in 61 EM (EMI) patients and 30 control subjects. Twenty patients with many of the symptoms of EM were enrolled as an active control group (EMII). Using laser Doppler flowmetry, basal skin erythrocyte flux (SkEF) and the hyperaemic response to local heating (44 degrees C) were measured. RESULTS: Compared with control subjects, basal SkEF was reduced at the toe (P < 0.001), index finger (P < 0.05), dorsal and plantar aspects of the foot (P < 0.01) in both patient groups and at the medial mid-calf (P < 0.05) in EMI patients. Both EM groups also had a significantly reduced maximum SkEF at the dorsum of foot and medial mid-calf (all P < 0.001) compared with control values. In a subset of patients and control subjects, transcutaneous carbon dioxide levels were raised in EMI patients (P < 0.02) compared with levels in control subjects. Toe temperature was significantly reduced in both EM groups compared with control subjects (both P < 0. 001). CONCLUSION: Our study indicates for the first time that there is a vasoconstrictor tendency in patients with EM, which may be related to functional or structural changes in skin microvessels. Thus, the previous hypothesis that the pathophysiology of EM relates to vasodilatation is not supported in our patients. We believe that, in EM, vasoconstriction precedes reactive hyperaemia, similar to that seen in Raynaud's phenomenon.

Adult↗