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H Tindall

Publications and source records attributed to H Tindall.

33 records · Page 2Linked to original sources

Urinary beta-thromboglobulin correlates with impairment of renal function in patients with diabetic nephropathy.

Beta-thromboglobulin (beta TG) is a platelet-specific protein and since its concentration in plasma rises when platelets are activated, it has been used as an indicator of platelet involvement in vascular disease. Since platelets might be involved in the pathogenesis of diabetic microvascular disease we measured urinary beta TG in 20 insulin-dependent diabetics with nephropathy and compared the results with those from 20 normal subjects. Measurement of beta TG in urine was undertaken to avoid errors induced by blood sampling and to gain information over a prolonged period using a single assay. Measurements were made of beta TG, beta 2-microglobulin and total protein in urine collected for 24 h and creatinine and beta 2 microglobulin in plasma. Survival of indium-111-labeled platelets was measured in nine patients. Urinary beta TG was significantly (p less than 0.02) increased in the 20 patients compared with 20 normal volunteers (median value 1.3 vs 0.8 microgram/24 h). There was a strong correlation between urinary beta TG excretion and plasma creatinine concentration (r = 0.8, p less than 0.0001) and plasma beta 2-microglobulin concentration (r = 0.9, p less than 0.0001). Urinary beta TG concentration did not correlate with platelet survival. The results indicate that although urinary beta TG is significantly increased in patients with diabetic nephropathy its concentration in urine correlates with indicators of glomerular filtration rather than with a test of platelet activation.

Adult↗

Renal scintigraphy and survival of indium-111-labelled platelets in patients with diabetic nephropathy.

Nine patients with overt diabetic nephropathy underwent renal scintigraphy and measurement of platelet survival time using indium-111-labelled platelets after treatment for six weeks with aspirin-dipyridamole (990 mg/225 mg/day) or placebo in a double-blind cross-over study. External scanning of the renal areas at 16 and 40 h post-injection showed no excess activity of indium-111 relative to background. Mean platelet survival was within the published normal range at 9.1 +/- 0.6 days and 7.6 +/- 1.4 days using linear and gamma function analyses respectively. Treatment with aspirin-dipyridamole was without effect. The results suggest that significant platelet deposition in renal blood vessels is not an important factor in the pathogenesis of diabetic nephropathy.

Aspirin↗

Effect of dazoxiben, a thromboxane synthetase inhibitor on skin-blood flow following cold challenge in patients with Raynaud's phenomenon.

The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.

6-Ketoprostaglandin F1 alpha↗

Aspirin, prostacyclin and post-occlusive reactive hyperaemia in man.

We studied post-occlusive reactive hyperaemia using ecg-triggered mercury strain-gauge plethysmography in eight normal subjects treated with incremental doses of aspirin (27.5-1200 mg). The reactive hyperaemic response was measured in the finger (predominantly skin blood flow) and the calf (predominantly muscle). Concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in venous effluent blood from the hand by RIA, following arterial occlusion. Levels of TXB2 were significantly higher at 0-10 and 60-70 seconds (p less than 0.01), and 90-100 seconds (p less than 0.05) following release of occlusion compared to pre-occlusion values. However there was no significant change in concentrations of 6-oxo-PGF1 alpha and therefore by this method release of prostacyclin during reactive hyperaemia in the hand. Aspirin had no influence on finger or calf reactive hyperaemia 90 minutes after dosing, despite marked inhibition of platelet MDA production (75% after 110 mg, maximal inhibition after 1200 mg). These data provide no support for the hypothesis that prostacyclin is involved in the determination of the post-occlusive reactive hyperaemic response in the finger and calf in man.

6-Ketoprostaglandin F1 alpha↗

Aspirin, dipyridamole and platelet survival in patients with diabetes mellitus.

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P less than 0.001) prolongation of platelet survival from 7.3 +/- 0.2 (mean +/- SEM days to 8.4 +/- 0.1 days. 4. In group II patients, when compared with the mean placebo result of 7.2 +/- 0.2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P less than 0.01) longer only after high-dose-aspirin/dipyridamole (9.8 +/- 0.5 days) but not after low-dose-aspirin/dipyridamole (8.3 +/- 0.5 days) or aspirin alone (7.3 +/- 0.3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

Adult↗

The influence of a combined oral contraceptive pill and menstrual cycle phase on digital microvascular haemodynamics.

1. Nailfold capillary pressure, digital blood flow and skin temperature have been measured on days 7, 14, 21 and 28 of the menstrual cycle in 10 women on a combined oral contraceptive pill and 10 control subjects with normal menstrual cycles. 2. Capillary pressure and digital blood flow were statistically significantly higher in the group taking an oral contraceptive pill compared with control subjects. 3. Capillary pressure values for women failed to show the same positive correlation with skin temperature previously described in normal men. 4. The results are interpreted as evidence for a powerful modulating influence of sex steroids on digital microvascular haemodynamics.

Adult↗

Changes in thrombin-stimulated platelet malondialdehyde production during the menstrual cycle.

Forty normal women had thrombin-stimulated platelet malondialdehyde (MDA) production measured during their menstrual cycle. Twenty women in this group were taking the combined oral contraceptive pill (OCP). Platelet MDA production was found to fall by 30% during normal menstruation and the week when the subjects were not taking a combined OCP, but it remained constant throughout the remainder of the cycle. No significant change in initial platelet aggregation response to stimulation by thrombin, change in plasma thrombin clotting time, plasma heparin neutralising activity (HNA), or plasma antithrombin III (AT-III) activity was seen when the platelet MDA production was reduced. The bleeding time results showed some variation throughout the menstrual cycle but these did not appear to be related to the variation in platelet MDA production.

Adult↗

Higher levels of microproteinuria in Asian compared with European patients with diabetes mellitus and their relationship to dietary protein intake and diabetic complications.

Asian patients with diabetes have a higher prevalence of renal disease than their European counterparts. The aim of the study was to investigate the pattern of the renal excretion of proteins in 70 Asian and 70 European patients with diabetes and to relate it to dietary intake of protein and prevalence of diabetic complications. Compared with matched Europeans, Asian patients had an increased urinary excretion of albumin and transferrin (p < 0.02) with 14 Asians and 6 Europeans having significant microalbuminuria (> 30 micrograms min-1). In 12 Asians and all 6 Europeans this was associated with complications from diabetes, particularly vascular. Asian patients had significantly more ischaemic heart disease (p < 0.001) but less neuropathy (p < 0.001) and retinopathy (p < 0.05) than their matched European counterparts. Asian diets were lower in protein (median (range) Asian vs European: 12.5% (6-29%) vs 19% (11-27%); p < 0.01) and carbohydrate but higher in fat than European diets. There was no correlation between dietary protein intake and excretion of any of the urinary proteins measured. However, a significant correlation was found in Asians between protein intake and length of residence in the UK (p < 0.005). Unless ways to reduce complications can be found then future allocation of resources will need to take this into consideration in areas with large Asian communities.

Adult↗