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Biomedical subjects

C M Florkowski

Publications and source records attributed to C M Florkowski.

18 recordsLinked to original sources
PubMed1992

Approaches to the management of hypercholesterolaemia.

Patients with hypercholesterolaemia need to be carefully evaluated for underlying secondary or genetic causes. All such subjects require dietary advice. Those with total cholesterol levels persistently in excess of 6.5 mmol/l despite diet, and in the presence of multiple cardiac risk factors may need drug therapy. Drug therapy is likely to be life-long and the potential benefits need to be carefully assessed against the long-term safety of the agents employed.

Bezafibrate↗
PubMed1992

Hypertension, coronary artery disease and insulin resistance--linked disorders with an impact on treatment.

Coronary artery disease is a very common disorder for which hypertension is a well-recognized risk factor. However many trials of antihypertensive therapy have failed to demonstrate a reduction in the incidence of coronary events. One explanation is that hypertension is a disorder associated with hyperinsulinaemia, obesity and non-insulin dependent diabetes. Furthermore certain antihypertensive drugs, notably thiazide diuretics, increase the hyperinsulinaemia and thereby increase one of the other coronary risk factors. In this review the links between hypertension and hyperinsulinaemia are explored and the mechanisms whereby an increased plasma insulin can lead to the more rapid development of coronary artery disease are explained. These observations may influence the choice of drugs used to treat hypertension.

Arteriosclerosis↗
PubMed1992

Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities.

Two patients with carbon monoxide poisoning are presented, both of whom suffered rhabdomyolysis complicated by acute renal failure. One patient, an attempted suicide, developed a compartment syndrome of the right thigh that required fasciotomy and recovered after a period of hemofiltration and hemodialysis. Muscle biopsy appearances were consistent with partial muscle infarction. The other patient, rescued from a smoke filled room, exhibited raised creatine kinase but no evidence of muscle swelling. He developed anuric renal failure and adult respiratory distress syndrome and died despite maximum intensive care. Muscle biopsy showed early evidence of muscle necrosis. In both cases there was a marked reduction of enzyme activities in the muscle biopsy consistent with metabolic derangement. Although there was a clinical compartment syndrome in the first case, there was no muscle swelling at the time of biopsy or subsequently in the second case. A direct toxic effect of carbon monoxide may thus have been an important mechanism contributing to the muscle necrosis in the second case, although local ischemia may have been an exacerbating factor in the first case.

Acute Kidney Injury↗
PubMed1991

Pathophysiology of hypertension in diabetes mellitus--implications for management.

A variety of mechanisms may lead to the initiation and progression of hypertension in patients with diabetes mellitus; an understanding of their nature may provide a rational basis for the choice of management. Nevertheless, a decision on the management of an individual patient remains a matter of clinical skill and judgement.

Antihypertensive Agents↗
PubMed1991

Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy.

Increased flux through the polyol pathway mediated by the enzyme aldose reductase may be associated with the development of diabetic neuropathy. Fifty-four diabetic patients (median age 56 yr, range 25-65 yr) with chronic neuropathic symptoms were randomly allocated to placebo or aldose reductase inhibition (300 or 600 mg ponalrestat ICI 128436) groups for 24 wk. Patients with vibration perception thresholds (VPTs) greater than 35 V at the great toe or thermal difference thresholds (TTs) greater than 10 degrees C on the dorsum of the foot were excluded from the trial. No significant changes were observed in symptoms of pain, numbness, or paresthesia between ponalrestat and placebo groups, and there were no improvements in VPT or TT at several sites. Posterior tibial nerve conduction velocity changed from 35.3 +/- 4.9 m/s at baseline to 33.4 +/- 4.0 m/s at 24 wk (NS) with placebo compared with 37.6 +/- 5.6 vs. 37.2 +/- 8.7 m/s (NS) with 300 mg ponalrestat and 34.5 +/- 6.1 vs. 36.2 +/- 6.8 m/s (NS) with 600 mg ponalrestat. Further studies are indicated with intervention at an earlier stage in the evolution of neuropathy and for longer periods.

Aldehyde Reductase↗
PubMed1990

Raised dopamine metabolites in a case of malignant paraganglioma.

This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension.

Adult↗
PubMed1989

The human red blood cell glyoxalase system in diabetes mellitus.

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.

Adult↗
PubMed1988

Microalbuminuria in diabetic subjects with chronic peripheral neuropathy.

Fifty-five patients with chronic peripheral neuropathy, 31 with and 24 without retinopathy, had albumin excretion rates determined on 2-h supine urine collections on three occasions by a radioimmunoassay method. Four patients with retinopathy had albustix-positive proteinuria and were excluded from subsequent analysis. Microalbuminuria was found in 20 of the 27 patients with retinopathy compared with 10 of the 24 patients with neuropathy alone. The mean albumin excretion rate (AER) was higher in neuropathic patients with retinopathy than in those patients with neuropathy alone (41.2 +/- 40.3 vs 18.8 +/- 33.2 micrograms/min, P less than 0.01). Multivariate analysis of the data was performed and this revealed a correlation coefficient of R2 = 0.33 (P less than 0.01) for AER as the dependent variable with respect to the independent variables HbA1, systolic blood pressure and known duration of diabetes. There was, however, no significant contribution separately of these individual variables to the regression equation. Microalbuminuria was significantly associated with retinopathy although almost half of the patients with neuropathy alone had microalbuminuria. The association between microalbuminuria and neuropathy even in the absence of retinopathy provides support for a microvascular element in the pathogenesis of diabetic neuropathy.

Albuminuria↗
PubMed1988

Effect of gliclazide on thromboxane B2, parameters of haemostasis, fluorescent IgG and lipid peroxides in non-insulin dependent diabetes mellitus.

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.

Aged↗
PubMed1988

Serum antioxidant activity in diabetes mellitus.

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.

Aged↗
PubMedDate not supplied

Increased diene conjugates in diabetic subjects with microangiopathy.

Free radicals are highly reactive unstable chemical species which have been implicated in the vascular damage associated with several disease states. Diene conjugates, probable products of free radical activity on lipids, were measured spectrophotometrically in 26 diabetic patients with microangiopathy, 36 uncomplicated diabetic patients, and 36 healthy controls. Total diene conjugates and diene conjugate to triglyceride ratios were significantly elevated in diabetic patients with microangiopathy (0.57 +/- 0.08 and 0.31 +/- 0.14 OD units/ml respectively; mean +/- SD) when compared with patients without complications (0.32 +/- 0.10, p less than 0.001, and 0.17 +/- 0.06, OD units/ml, p less than 0.011). There was no difference in total diene conjugation and their ratio to triglycerides between healthy controls and uncomplicated diabetic patients and the results were not influenced by the type of diabetes or level of diabetic control. Diene conjugate ratios repeated in 14 patients on two occasions, 6 weeks apart, with stable metabolic control were consistent. Increased diene conjugation suggesting increased free radical activity is associated with microangiopathy and this may have pathogenetic implications.

Adult↗
PubMedDate not supplied

Urinary transferrin excretion in type 1 (insulin-dependent) diabetes mellitus.

Urinary excretion of transferrin and albumin was studied by radioimmunoassay in 47 adult patients with Type 1 diabetes and 28 control subjects. Median (range) urinary transferrin excretion rate was significantly elevated in the diabetic group 0.58 (0.02-2663.3) micrograms min-1 compared with the control group 0.04 (0.01-0.28) micrograms min-1, p less than 0.001. Urinary transferrin:creatinine ratios (x 10(2)) were different in diabetic 47 (0.6-958.0) micrograms mmol-1 and control groups 0.7 (0.06-2.3) micrograms mmol-1, p less than 0.001). There were correlations between urinary transferrin and albumin excretion rates in diabetic (r = 0.78, p less than 0.001) and control groups (r = 0.81, p less than 0.05). Forty (85%) diabetic patients had elevated transferrin excretion rates, 18 (38.3%) had elevated albumin excretion rates. All diabetic patients with elevated albumin excretion rates had elevated transferrin excretion rates. Twenty-one (77.8%) of the patients with normal albumin excretion rates had elevated transferrin excretion rates. Urinary excretion of N-acetyl-beta-D-glucosaminidase was greater in diabetic patients than control subjects (142 vs 58 mumol h-1 l-1, p less than 0.001). There were correlation between transferrin and N-acetyl-beta-D-glucosaminidase excretion (r = 0.67, p less than 0.01) and albumin and N-acetyl-beta-D-glucosaminidase excretion (r = 0.63, p less than 0.01) in the diabetic group. Elevated urinary transferrin excretion rate may be a marker for renal dysfunction in diabetes mellitus.

Acetylglucosaminidase↗