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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
PubMed1992

Relationship between the extent of coronary artery disease and indicators of free radical activity.

Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p less than 0.001 and p less than 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461 microM IQR 1348-1709, p less than 0.002) compared with the controls (median 1754 microM IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p less than 0.001 and p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effects of gliclazide on platelet reactivity and free radicals in type II diabetic patients: clinical assessment.

In vitro studies have demonstrated that gliclazide has free radical scavenging and antiplatelet activities. To assess this clinically, we studied gliclazide in a blinded, randomized, glibenclamide-controlled trial in 30 type II diabetic patients with retinopathy. All patients had been taking glibenclamide for more than 12 months before being randomized to receive either an equipotent dose of gliclazide or to continue on glibenclamide. Diabetic control was not modified. The patients were well matched at randomization (mean age, 58 years; duration of diabetes, 8 years; 20 males; mean hemoglobin A1 [HbA1], 8.6%) and their degree of diabetic control was not altered during the trial. Free radical activity was assessed as oxidative status by plasma thiols (PSH), lipid peroxides (MDA-LM), and red blood cell superoxide dismutase activity (SOD). Platelet aggregation in whole blood to collagen (Plt-ag) was used as the measure of platelet reactivity. There were no differences between these measurements at baseline. At 3 months, the oxidative status and platelet aggregation in the gliclazide group had improved significantly compared with baseline and had also showed significant differences in all parameters when compared with the glibenclamide group. Therefore, comparing gliclazide with glibenclamide-treated patients at 3 months, we found: PSH, 458 +/- 38 versus 414 +/- 34 mumol/L, P less than .004; MDA-LM, 7.0 +/- 0.6 versus 8.3 +/- 0.8 mumol/L, P less than .0002; SOD, 152 +/- 36 versus 123 +/- 15 micrograms/mL, P less than .016; Plt-ag, 50.8 +/- 24 versus 72.3% +/- 15%, P less than .006. These changes were maintained at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of dialyzer geometry during hemodialysis with cuprophane membranes.

The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cutaneous vascular responses and thermoregulation in relation to age.

1. Sympathetic vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge were assessed in fingertip skin in relation to age and were correlated with vasoconstrictor ability during body cooling. The above relationship was also examined in diabetic patients in whom vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge had been shown previously to be markedly impaired. 2. Vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge, measured by laser Doppler flowmetry, were significantly reduced in the elderly group, although individual responses varied from normal to absent, and they also had a considerably greater variability as measured on three separate occasions than seen in young subjects. Discriminant analysis showed that, from each of three occasions, 65% of vasoconstrictor responses were abnormal in the elderly group. 3. Body cooling was performed by reducing the environmental temperature from 40 degrees C to 12 degrees C, and the time taken for blood flow to fall to 75%, 50% and 25% of the pre-cooling level (VC75, VC50, VC25, respectively) was calculated. Vasoconstriction was rapid in young subjects and was consistent with good vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge. In the elderly group, vasoconstriction was slower, but only the VC25 value differed significantly [elderly group, 13.3 (7.9-31.0) min, young group, 5.7 (2.7-15.5) min; median (interquartile range); P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Prothrombotic effect of erythropoietin in dialysis patients.

Thrombin-antithrombin III complex concentrations (TAT-III) were measured in 18 anaemic haemodialysis patients treated with erythropoietin (Epo) and in four haemodialysis patients treated with i.v. iron dextran. There was a significant early increase in thrombin-antithrombin III in erythropoietin-treated patients which appeared to be independent of the response to erythropoietin (Epo responders (n = 14), pretreatment TAT-III median (range) 3.10 (2.70-9.10) micrograms/l; maximum TAT-III 19.48 (11.18-60.00) micrograms/l, P less than 0.001, Wilcoxon; Epo non-responders (n = 4), pretreatment TAT-III 3.15 (2.90-4.50) micrograms/l, maximum TAT-III 16.00 (10.31-36.12) micrograms/l, P less than 0.001). This was not seen in iron-dextran-treated patients (Pretreatment TAT-III 2.05 (1.90-9.48) micrograms/l, maximum TAT-III 5.60 (2.10-14.50) micrograms/l). The change was not related to haemoglobin, erythropoietin dose, or method of administration, and was transient in nature, thrombin-antithrombin III returning to pretreatment values after approximately 6 months in all patients (Epo responders 6.0(4.0-9.0) months, TAT-III 2.47 (1.30-9.23) micrograms/l; Epo non-responders 7.0 months, TAT-III 5.04 (2.10-7.00) micrograms/l). Increased thrombin-antithrombin III complex may reflect an effect of erythropoietin on microcirculatory factors, which could be relevant to the occurrence of adverse events during treatment.

Adult↗
PubMed1992

Further evidence of increased polymorphonuclear cell activity in patients with Raynaud's phenomenon.

The role of polymorphonuclear cells (PMNs) in the pathophysiology of ischaemic vascular disease has been increasingly recognized in recent years. Activated PMNs may physically obstruct blood flow. Subsequent release of reactive oxygen radicals and lytic enzymes lead to continued damage. Previous studies have shown increased white cell activity in patients with secondary Raynaud's syndrome (RS). However, whether this is related to the underlying condition or to digital vasospasm is not clear. Using a more physiological whole blood PMN aggregation assay, we assessed PMN activity in 38 patients with severe Raynaud's phenomenon (RP) [16 had systemic sclerosis (SSc) and secondary RS; 22 had RP alone and no other features of a connective tissue disease]. Additionally, plasma levels of malondialdehyde (MDA), an indicator of free radical activity, were measured. Results were compared with those obtained from 56 matched volunteers. In order to assess if changes in PMN activity was directly related to digital vasospasm, patients were asked to record the duration and frequency of their Raynaud's attacks during a 2-week period using a pocket sized diary. Correlation between these clinical variables of Raynaud's severity and white cell activity was assessed. Patients with RP, both with and without SSc, showed a significantly greater fall in single PMN count when compared with control subjects [SSc associated RS 48.2 (41.4-56)% versus control, P = 0.04; RP alone 49.3 (46.8-52.1)% versus control, P = 0.01 (Mann-Whitney U-test)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Beta-adrenoceptor antagonists enhance white blood cell aggregation in patients with ischaemic heart disease.

The effects of beta-adrenoceptor antagonists, calcium channel blockers and long acting nitrates on white blood cell (WBC) aggregation were studied in patients with ischaemic heart disease. WBC aggregation was significantly increased by beta-adrenoceptor antagonists (P = 0.011) but was unaffected by either calcium channel blockers or long acting nitrates. Enhanced WBC aggregation promotes microvascular occlusion and damage.

Adrenergic beta-Antagonists↗
PubMed1992

Detection of microvascular impairment in type I diabetics by laser Doppler flowmetry.

The use of a laser Doppler flowmeter to detect microcirculatory impairment and abnormalities in sympathetic neural control of blood flow in the hands and feet was evaluated. Measurements were carried out in 15 insulin dependent diabetic patients with retinopathy, 14 uncomplicated diabetics and 15 normal subjects. Three tests were assessed (1) the hyperaemic response of the skin microcirculation to local heating at 44 degrees C; (2) the reactive hyperaemic response of the skin microcirculation to 2 min arterial occlusion; and (3) the peripheral vasoconstrictor reflexes to cold challenge and inspiratory gasp. Tests (1) and (2) were applied to the dorsum of the hand and foot and test (3) to the pulp of the fingertip and toe. All tests were carried out with the subjects peripherally vasodilated by indirect heating. At the hand no differences were found between the groups for any of the measures. The hyperaemic response to local heating at the dorsum of the foot showed that the maximum flow in complicated diabetics was significantly lower than that in uncomplicated patients (P less than 0.01) and in normal subjects (P less than 0.002). A new measure, the time for flow to increase to 3 times basal flow, was longer in the complicated group compared with the uncomplicated (P less than 0.02) and the normal groups (P less than 0.001). This test also showed that the response in the uncomplicated group was slower than in the normal group (P less than 0.01). The post-occlusive hyperaemic response did not differ between groups. Measurement of vasoconstrictor reflexes showed that the complicated group had a poorer response to cold challenge at the big toe than the uncomplicated group (P less than 0.02) and the complicated group generally tended to have poorer responses than the other two groups. In conclusion, we have found that the hyperaemic response to local heating can detect microvascular impairment in diabetes before other complications become apparent and that the vasoconstriction test may be able to identify individuals with peripheral sympathetic neuropathy.

Adult↗
PubMed1992

White blood cell activation in Raynaud's phenomenon of systemic sclerosis and vibration induced white finger syndrome.

Systemic sclerosis (SSc) and vibration induced white finger syndrome (VWF) are common causes of secondary Raynaud's phenomenon. Previous studies have suggested an increase in inflammation in patients with SSc. Vibration induced white finger syndrome occurs in workers exposed to vibration and is now a prescribed disease. In VWF, although it is recognised that vibration can cause direct damage to blood vessels, it does not explain why only some workers are affected. It is possible that an inflammatory process develops in these patients in the same way as is seen in SSc. Leukotriene B4, produced mainly by polymorphonuclear cells, is a potent mediator of inflammation. The plasma thiol concentration shows the degree of oxidation of plasma and a decreased concentration indicates the increased production of free radicals which are capable of oxidative damage. In this work, the white blood cell (WBC) production of leukotriene B4 and plasma thiol concentrations were measured in patients with SSc and VWF. Fifty nine patients were studied: 34 had SSc and 25 had VWF. The results were compared with 25 matched normal controls and are expressed as the median and range. After stimulation of the polymorphonuclear cells with calcium ionophore A23187 (1 microgram/ml), patients with SSc and VWF were found to have significantly increased leukotriene B4 production (23.5 (14.4-44.0) and 26 (14.4-39.4) ng/10(6) cells, respectively) compared with normal controls (17.2 (6.0-38.0) ng/10(6) cells). The plasma thiol concentration was shown to be significantly lower in patients with SSc and VWF (445 (375-475) and 450 (417-510) mumol/l, respectively) compared with normal controls (480 (418-555) mumol/l). Our results show increased leukotriene B4 production and increased free radical activity in patients with SSc and VWF. Although previous indirect evidence has suggested increased WBC activity in patients with SSc, this is reported directly here for the first time. In addition, the possibility of an inflammatory process occurring in patients with VWF, as shown here, has not previously been studied. This may be a further mechanism to explain the poor circulation in the fingers of these patients.

Adult↗
PubMed1992

Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers.

Previous studies have demonstrated circadian rhythms in the onset of thrombotic events, which occur most commonly in the morning, and also in the fibrinolytic activity of the blood which has a peak in the evening and a trough in the morning. There has recently been increasing interest in the role of white blood cells (WBCs) and free radicals (FRs) in thrombosis. No one has yet investigated the potential circadian variation of WBC aggregation and FRs in humans. We studied the circadian rhythm of WBC aggregation and FR status in 10 healthy male volunteers. Six blood samples were collected at 4 hourly intervals from 12:00 (mid-day) until 08:00 the following morning. The volunteers carried out normal daily activities until 00:00 at which time they went to bed and they remained in bed until 08:00. The following were measured on each sample: WBC aggregation; thiobarbituric acid reactive substances (TBARs), plasma thiols (PSH), red cell lysate thiols (LSH), glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of FR activity. The following parameters demonstrated significant circadian rhythms, WBC aggregation p less than 0.001, TBARs p less than 0.015, PSH p less than 0.001, LSH p less than 0.002. WBC aggregation was lowest at 09:00 and highest at 00:00-04:00. TBARs and PSH both had a peak at 16:00 and a trough at 04:00. LSH had a peak at 12:00 and a trough at 08:00. As the behaviour of WBCs and FR status influence the flow properties of blood, a circadian rhythm in WBC function and FR status may contribute to the time of onset of thrombotic diseases. Moreover, with many studies being currently undertaken in this area, our work indicates the need to standardize sample times.

Adult↗
PubMed1992

Dialysis efficiency in continuous ambulatory peritoneal dialysis patients treated with erythropoietin.

OBJECTIVE: To determine the effect of subcutaneous erythropoietin treatment on dialysis efficiency in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Dialysis efficiency, platelet and white cell aggregation, and red cell deformability were measured monthly for six months in nine anaemic CAPD patients treated with erythropoietin, and on a single occasion in seven control CAPD patients with intrinsically high haemoglobin concentrations. SETTING: Renal dialysis unit. PATIENTS: Nine patients stable on CAPD for a minimum of six months and with haemoglobin concentrations less than 8.5 g/dl were treated with erythropoietin. Seven CAPD patients matched for age and renal function, with haemoglobins greater than 9.0 g/dl served as controls. RESULTS: Daily peritoneal clearances and net ultrafiltration volumes were unchanged when haematocrit increased from 25.0 +/- 2.2% to 36.5 +/- 3.5%. Spontaneous whole blood platelet aggregation was significantly increased from week twelve (pre-treatment aggregation 46 +/- 23%; 12 weeks: 67 +/- 19%, p less than 0.05; 16 weeks: 64 +/- 19%, p less than 0.01; 20 weeks: 71 +/- 16%, p less than 0.01; 24 weeks: 73 +/- 10%, p less than 0.01). CONCLUSIONS: The increase in haematocrit and platelet aggregation associated with erythropoietin treatment did not affect peritoneal clearances or ultrafiltration capacity.

Anemia↗
PubMed1992

Lipid peroxidation and antioxidants in continuous ambulatory dialysis patients.

OBJECTIVE: Oxidative cell damage due to the production of free radical species has been implicated in the pathogenesis of cardiovascular disease for which dialysis patients are at increased risk. Plasma lipid peroxides (malon-dialdehyde), the antioxidants plasma albumin thiol, and red cell superoxide dismutase (SOD) were therefore measured in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 20 hemodialysis patients, and 30 normal controls. SETTING: Renal dialysis unit. RESULTS: Malondialdehyde (MDA) concentrations were significantly higher in dialysis patients compared to controls (p less than 0.001) and were significantly higher in CAPD patients compared to hemodialysis patients, p less than 0.001 (CAPD, median and range: 11.25 (8.4-15.5) nmol/mL; hemodialysis: 8.75 (7.0-12.6) nmol/mL; controls: 6.65 (5.2-9.6) nmol/mL). Plasma thiol and red cell SOD were significantly lower in dialysis patients compared to controls, but there was no significant difference between CAPD and hemodialysis patients (CAPD thiol: 333.5 (282-480) mumol/L; hemodialysis thiol: 344 (203-468) mumol/L; control thiol: 421.5 (351-504) mumol/L; CAPD SOD: 78.2 (42.4-112.8) u/1/2 mL red cells; hemodialysis SOD: 89.4 (44.6-121.1) u/1/2 mL red cells; control SOD: 96.8 (66.8-153.4) u/1/2 mL red cells). Red cell SOD was significantly negatively correlated with duration of dialysis in CAPD patients (r = -0.683, p less than 0.01). CONCLUSION: In dialysis patients there is indirect evidence for increased free radical activity, which may be further influenced by the mode of dialysis.

Erythrocytes↗
PubMed1991

Erythropoietin and spontaneous platelet aggregation in haemodialysis patients.

Erythropoietin significantly, reversibly, and reproducibly increased in-vitro whole-blood spontaneous platelet aggregation in 15 patients on haemodialysis. During erythropoietin treatment, spontaneous platelet aggregation was significantly higher in these subjects than in non-uraemic controls; concomitant treatment with 300 mg aspirin daily reversed platelet hyperaggregability. Erythropoietin may promote thrombosis by an effect on platelet function.

Anemia↗
PubMed1991

Gliclazide: a general free radical scavenger.

Free radical mechanisms have been implicated in diabetic microangiopathy. Agents that scavenge free radicals may be beneficial. We assessed the scavenging ability of two sulphonylureas, gliclazide and glibenclamide, in vitro. The assay which employs o-dianisidine sensitised by riboflavin can be used to distinguish between superoxide scavengers and general scavengers. The former species lead to an augmentation while the latter has an inhibitory effect. The drugs were added in final concentrations of 0.5, 1.0, 2.5 and 5.0 micrograms/ml. The percentage inhibition (mean +/- S.D.) for each concentration of gliclazide respectively was 11.0 +/- 2.5%, 20.8 +/- 2.9%, 31.4 +/- 2.2% and 47.2 +/- 0.8%. Glibenclamide had no scavenging effects. The results demonstrate that gliclazide is a powerful general free radical scavenger in vitro. We postulate that this scavenging quality of gliclazide may be important in diabetes.

Dianisidine↗
PubMed1991

The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome.

Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 degrees C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 degrees C followed by rewarming to 40 degrees C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗