Ultrasound boosts growth of interventional imaging.
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Biomedical subjects
Publications and source records attributed to A F Jones.
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To find out whether the hypophosphataemia in paracetamol poisoning is due to renal loss of phosphate, serum phosphate concentrations were correlated with indices of hepatotoxicity in 273 patients who had taken an overdose of paracetamol, and the renal handling of phosphate was examined in another 40 patients. Hypophosphataemia was a feature of paracetamol poisoning, whether hepatotoxicity was present or not. It correlated with the degree of hepatic damage and was not influenced by glucose infusions. Serum phosphate correlated with renal threshold phosphate concentration, so renal loss rather than intracellular redistribution of phosphate seems to be the reason for the hypophosphataemia in paracetamol overdose, and it correlates well with other indices of severity of poisoning.
Methylglyoxal and other alpha-oxoaldehydes are formed from glycolytic intermediates and may be involved in the development of diabetic microangiopathy. Glyoxalase I and glyoxalase II metabolise methylglyoxal to D-lactic acid, via the intermediate S-D-lactoylglutathione. The activities of the glyoxalase enzymes and the concentrations of methylglyoxal and S-D-lactoylglutathione were measured in erythrocytes of 45 control and 85 diabetic subjects (41 with retinopathy and 44 uncomplicated). The concentration of S-D-lactoylglutathione was increased in diabetic patients vs. controls (21.4 +/- 9.3 vs. 12.4 +/- 4.8 mumol/l, P less than 0.001), as was methylglyoxal (3.6 +/- 2.3 vs. 1.4 +/- 0.2 mumol/l, P less than 0.001). There were no significant differences in the activities of glyoxalase I and glyoxalase II between diabetic patients and controls. For insulin-dependent patients only, those without retinopathy had a higher activity of glyoxalase II than those with retinopathy (P less than 0.05). A group of age- and duration-matched insulin-dependent diabetic patients with retinopathy also had a higher activity of glyoxalase I compared with a group of diabetic patients without retinopathy (P less than 0.025). This study provides evidence for elevated concentrations of oxoaldehydes in diabetes mellitus which might have pathogenic significance.
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Non-enzymatic glycosylation of long-lived proteins results in a characteristic fluorescence, known as protein 'browning'. The degree of fluorescence of skin collagen correlates with retinopathy in diabetes. We have therefore measured the fluorescence of serum albumin and IgG by a sensitive HPLC technique in 69 diabetic patients, 38 with retinopathy and 31 without complications, and in 26 age-matched controls. The fluorescence of the IgG fraction, calculated as the ratio of fluorescence (excitation 360 nm, emission 454 nm) to optical density (280 nm), was elevated in diabetic patients with retinopathy (1.5 +/- 0.5) compared with those without retinopathy (1.1 +/- 0.2, p less than 0.005) and control subjects (1.1 +/- 0.2, p less than 0.005). The fluorescence ratio for the albumin fraction was increased in all diabetic patients (11.2 +/- 2.7) compared with control subjects (8.9 +/- 1.5, p less than 0.001). There was no significant difference in the fluorescence ratios of albumin in those with and without retinopathy. The fluorescence of serum albumin and IgG were not significantly correlated with serum protein glycosylation measured by the fructosamine method.
Ten trauma patients and 13 burns patients were studied intensively for the first 36 h and subsequent 6 days post injury in order to investigate the mechanism of trauma and burn associated proteinuria. Burns patient's initial maximum proteinuria occurred between 4 and 8 h post injury, whilst trauma patients showed greatest proteinuria within 4 h. In both groups coexisting myoglobinuria or marked elevation of serum renin activity was not found during the first 36 h. Following admission serum lipid peroxides rose in burns patients reaching a maximum between 2 and 8 h following injury, after which levels fell rapidly; in contrast trauma patient's values were initially within normal limits, but rose sharply after 12 h with peaks occurring between 16 h and 7 days post injury. Some patients within both groups showed a recurrent protein leak 2 to 5 days post injury. The data suggest that myoglobinuria or raised renin levels do not play an important role in trauma associated proteinuria.
The oxidase activity of caeruloplasmin towards Fe II (ferroxidase) appears to be of physiological significance both in iron metabolism and as a serum anti-oxidant. We have developed an automated assay for ferroxidase using a centrifugal analyser. The method is quick and precise, and is not subject to interference by haemolysis, jaundice or lipaemia. Ferroxidase activities correlate significantly with caeruloplasmin and copper concentrations. Normal reference ranges have been measured.
Abnormalities of platelet aggregation, and increased levels of lipid peroxides and denatured proteins have been implicated in the pathogenesis of diabetic microangiopathy. Seventeen non-insulin dependent diabetics (mean age 65.7) on established sulphonylurea therapy were converted to an equivalent dose of gliclazide. They were studied at baseline and intervals to 36 weeks. Thromboxane B2 (TXB2) and beta thromboglobulin (beta TG) were measured by radioimmunoassay. Lipid peroxides were measured as total diene conjugates (DC) by scanning UV spectrophotometry and thiobarbituric acid reactivity (TBA) by absorbance at 532 nm. Oxidation products of proteins were represented by fluorescence/UV ratio of immunoglobulin G (*IgG) separated from serum by HPLC. Glycaemic control remained stable throughout the study. TXB2 fell from 734 +/- 233 ng/l at 0 weeks to 488 +/- 155 at 36 weeks, p less than 0.001 and beta TG from 120 +/- 70 ng/ml to 48 +/- 18 at 24 weeks, p less than 0.005. Lipid peroxides fell between 0 and 36 weeks; DC from 0.71 +/- 0.28 to 0.32 +/- 0.09, p less than 0.001 and TBA from 29.6 +/- 22.4 to 4.0 +/- 2.2, p less than 0.001. Fluorescent IgG ratio fell from 1.44 +/- 0.36 to 0.32 +/- 0.07, p less than 0.001. This data provides evidence for a specific action of gliclazide on thromboxane synthesis and platelet aggregation. This is independent of glycaemic control and may in part be mediated by the observed fall in lipid peroxides.
Free radical medicated oxidative damage has previously been implicated in the pathogenesis of diabetic microangiopathy. Caeruloplasmin and transferrin act as antioxidants in serum by oxidizing and chelating ferrous iron which could otherwise act as a catalyst in free radical reactions. We have measured the serum anti-oxidant activity in 67 diabetics, 25 of whom had retinopathy and in 37 controls. Serum iron concentrations were normal in diabetics in comparison with controls (21.5 +/- 10 v 19.5 +/- 6.7 mumol/L) although transferrin and iron binding capacity were increased in the diabetics (3.7 +/- 0.8 v 2.9 +/- 0.9 g/L, p less than 0.001 and 69.9 +/- 10.8 v 59.0 +/- 14 mumol/L, p less than 0.002 respectively). Caeruloplasmin, measured by its ferroxidase activity, was increased in both male (46 +/- 11 v 36 +/- 9 mu/mL, p less than 0.002) and female diabetics (57 +/- 13 v 47 +/- 11 mu/mL, p less than 0.002). Ferritin was also increased in both male (124 +/- 113 v 44 +/- 38 ng/mL, p less than 0.001) and female diabetics (132 +/- 118 v 25 +/- 12 ng/mL, p less than 0.001). The presence of retinopathy, the degree of glycaemic control and duration of diabetes had no effect on these findings. We conclude that increased concentrations of iron-oxidizing and iron-binding proteins occur in diabetic serum, and that the increased serum antioxidant activity may be a response to oxidative stress.
Evidence for free radical involvement in pathological processes is often indirect and frequently depends upon the detection of characteristic changes in tissue constituents, particularly polyunsaturated lipids. Free radical attack on protein leads to specific oxidative changes in their constituent amino acids, principally cysteine, tryptophan and tyrosine. This is associated with the induction of characteristic fluorescence (excitation 360 nm, emission 454 nm) and protein aggregation. This observation leads to a suitable assay for studying protein oxidation, and such fluorescent proteins may be relevant in the pathogenesis of diabetic microangiopathy and rheumatoid arthritis.
Recent evidence has suggested that diabetic microangiopathy is associated with increased free radical induced oxidative damage. Ascorbic acid (AA) is a free radical scavenger and using a specific HPLC method we have investigated its concentration and that of its oxidized metabolite dehydroascorbic acid (DHAA) in diabetic patients and matched normal controls. The findings have been related to the presence of microangiopathy and to glycaemic control. Ascorbic acid levels were significantly lower in diabetics (mean +/- SD 42.5 +/- 26.2 mumol/l) compared with controls (58 +/- 21 mumol/l p less than 0.02). Although there was no differences in DHAA levels between the groups the ratio DHAA/AA was increased in diabetics (0.72 +/- 0.8) compared with controls (0.4 +/- 0.2 p less than 0.05). There were no significant differences between insulin and non-insulin dependent patients in these measurements and there was no association with the presence of microangiopathy or poor glycaemic control. The plasma ratio DHAA/AA may be a reflection of increased oxidative stress and our results suggest that diabetics may be less able to prevent oxidative damage occurring due to their lower AA concentrations.
The fructosamine assay measures the degree of nonenzymatic protein glycation by virtue of the reducing properties of such proteins in alkaline conditions. We report the marked inhibitory effect of superoxide dismutase (EC 1.15.1.1) on the reducing activity both of protein glycated in vitro and of diabetic sera, indicating superoxide intermediacy in the fructosamine reaction. The free-radical intermediates may be of analytical significance when pathological and physiological changes in serum anti-oxidant activity occur. They may also be of pathological significance in diabetic microangiopathy and protein browning.
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An 82-year-old woman with the Canada-Cronkhite syndrome is described. The patient was unusual because of her age at presentation, favorable response to treatment with steroids and feeding jejunostomy, and associated hypothyroidism.
Aortic bypass grafting was performed in 100 consecutive patients with disabling manifestations of aortoiliac arterial occlusive disease. There were no operative deaths, graft infections, false aneurysms, or aortoduodenal fistulas. Of those patients whose superficial femoral arteries were patent, 95% had a good or excellent immediate functional result that was maintained in 89% on late follow-up. Of those whose superficial femoral arteries were occluded, 83% had a similar immediate result and 70% maintained this improvement. Graft limb patency was 89% after 36 months. Additional distal arterial reconstructions were ultimately required in 9% of all limbs, resulting in a good to excellent functional outcome for 93% of all our patients. We believe aortofemoral grafting remains the best method for the correction of aortoiliac occlusive disease.
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