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Biomedical subjects

J P Reckless

Publications and source records attributed to J P Reckless.

At least 55 records · Page 3Linked to original sources
PubMed1987

Glycaemic control in diabetic patients transferred from therapy with animal insulins to human crystalline zinc insulin of recombinant DNA origin: a multicentre study.

87 stable insulin-dependent diabetic patients from 6 diabetic clinics within the UK were transferred from their existing once or twice daily regimen of subcutaneous animal insulin to a similar regimen of human insulin of recombinant DNA origin in neutral soluble and crystalline zinc suspension formulations. Seven point blood glucose profiles, glycosylated haemoglobin concentrations and insulin dose were examined, in each patient, before and after 6 weeks therapy with human insulins. The 67 patients on twice daily insulin showed no significant change in mean blood glucose values or glycosylated haemoglobin but required a significantly higher dose of human crystalline zinc suspension than their previous long-acting animal insulin. In contrast the 17 patients on a once daily regimen experienced a significant deterioration in glycaemic control without a significant change in insulin dose or glycosylated haemoglobin. Three patients on twice daily insulin withdrew shortly after transfer to human insulin. The combination of human soluble and crystalline zinc suspension appears to be a more satisfactory substitute for animal insulin when used in a multi-dose regime rather than on a once daily basis.

Animals↗
PubMed1986

Paradoxical platelet behaviour in diabetic ketoacidosis.

Thrombotic events may occur in patients who present with severe uncontrolled diabetes or with diabetic coma. As a possible explanation for this, platelet function was investigated at presentation with diabetic ketoacidosis and during treatment in 10 patients. Concentrations of the platelet-specific proteins, platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) were elevated and fell towards normal with treatment. Despite evidence of increased aggregation in vivo, platelets from subjects with ketoacidosis were insensitive to adenosine 5'-diphosphate (ADP), sensitivity increasing with correction of ketoacidosis. Platelets from ketoacidotic diabetics were initially insensitive to the anti-aggregatory action of prostacyclin (PGI2) and became normal with treatment. Initial blood glucose concentrations correlated with log10 ADP concentrations (r = 0.72, p less than 0.01) and with log10 PGI2 ID50 (the PGI2 concentration required to half-inhibit ADP-induced aggregation) (r = 0.66, p less than 0.025). Glucose concentrations throughout the 2-week study period correlated with all log10 ADP concentrations (r = 0.32, p less than 0.005) and all log10 PGI2 ID50 concentrations (r = 0.51, p less than 0.001). The decrease in ADP sensitivity in ketoacidosis, paradoxical in view of the evidence of increased in vivo platelet aggregation, may result from an acquired platelet storage pool deficiency.

Adenosine Diphosphate↗
PubMed1985

Effects of acipimox, a nicotinic acid derivative, on lipolysis in human adipose tissue and on cholesterol synthesis in human jejunal mucosa.

The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10(-5) mol/l) fell by 40 and 25% respectively (P less than 0.025 and P less than 0.025) in the presence of acipimox (10(-5) mol/l). In submaximally stimulated adipose tissue (isoprenaline 10(-7) mol/l) acipimox (10(-4) mol/l) fully inhibited release of fatty acids (P less than 0.05) and glycerol (P less than 0.025) to basal rates. In unstimulated adipose tissue acipimox (10(-3) mol/l) reduced the rate of glycerol release (P less than 0.05), but not the rate of fatty acid release. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2-14C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2-14C]acetate incorporation into sterols from 8.7 +/- 2.1 (mean +/- standard error) to 3.7 +/- 1.0 pmol h-1 mg-1 of tissue (P less than 0.01). Acipimox at 10(-4)-10(-2) mmol/l had no consistent effect on cholesterol synthesis. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.

Adipose Tissue↗
PubMed1985

Limited joint mobility in diabetes mellitus.

The relationship of limited joint mobility and finger joint contractures in diabetics to age of onset, duration, and control of diabetes has not been established. We measured the mobility of metacarpophalangeal, wrist, elbow, and ankle joints and assessed the prevalence of finger joint contractures in 254 young diabetics and 110 controls. The presence of microvascular disease was assessed by ophthalmoscopy and urine analysis for proteinuria. An estimate of long-term diabetic control was obtained from a postal questionnaire. A generalised reduction in joint mobility was present in diabetics of all ages two years after diagnosis. The reduction in joint mobility in controls between the ages of 12 and 13 was exaggerated in the diabetics. Diabetics diagnosed before puberty were more severely affected than those with a postpubertal onset, independent of duration of diabetes. Finger joint contractures were a significant feature of longstanding diabetics (nine years or more duration) only.

Adolescent↗
PubMed1982

Diurnal variations in blood intermediary metabolites in mild gestational diabetic patients and the effect of a carbohydrate-restricted diet.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven non-diabetic women (group A) and in two groups of mild gestational diabetics, at diagnosis (group B, seven patients) and after treatment with a 150-g carbohydrate diet (group C, seven patients). Mean 24-h blood metabolite levels (+/- SD) in groups A, B and C were: glucose: 4.65 +/- 0.82, 5.35 +/- 3.06 and 5.40 +/- 1.7 mmol/l; alanine: 1.05 +/- 0.18, 1.14 +/- 0.42 and 0.78 +/- 0.22 mmol/l; alanine: 0.31 +/- 0.03, 0.31 +/- 0.10 and 0.27 +/-0.07 mmol/l; ketone bodies: 0.11 +/- 0.04, 0.19 +/- 0.05 and 0.26 +/- 0.15 mmol/l. Glucose levels were not significantly different between the groups. Ketone body levels were elevated in the diabetics prior to treatment (p less than 0.01) and rose higher on diet. Lactate levels were reduced on the diet (0.05 less than p less than 0.10). Abnormalities in the concentrations of total blood ketone body levels in gestational diabetics may be detrimental to fetal development and therapy should be designed to minimise changes in intermediary metabolites.

Alanine↗
PubMed1982

Studies of a variant very-low-density lipoprotein with an acquired deficiency of apolipoprotein C-II.

1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea-polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3-120 mmol/l) controls. 2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10-3H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera. 3. The efficacies of various VLDL as substrates fo activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared wtih an artificial triglyceride emulsion. 4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5-10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective. 5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37 degrees C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.

Adult↗
PubMed1982

Platelets from diabetic subjects show diminished sensitivity to prostacyclin.

Prostacyclin, an unstable metabolite of arachidonic acid metabolism, has been shown to have potent platelet antiaggregatory and vasodilator activity. Available evidence suggests that arterial prostacyclin production is diminished in the diabetic state. In this study we have examined the sensitivity of platelets from diabetic subjects to the antiaggregatory effects of prostacyclin in vitro and report that platelets from some diabetic patients show diminished sensitivity to the antiaggregatory effects of prostacyclin. Thus diabetic subjects may not only have diminished prostacyclin production but also their platelets may be less sensitive to its effects. These findings may help to explain the increase in vascular disease observed in diabetic patients.

Adenosine Diphosphate↗
PubMed1981

The effect of continuous subcutaneous insulin infusion and conventional insulin regimes on 24-hour variations of blood glucose and intermediary metabolites in the third trimester of diabetic pregnancy.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven diabetic women; first when optimally controlled using conventional insulin regimes and subsequently when controlled with continuous subcutaneous insulin infusion. Seven non-diabetic women also studied. Mean +/- SD 24 h metabolite levels in the diabetics before and during continuous subcutaneous insulin infusion and in the controls were respectively: glucose-5.8 +/- 1.2;5.0 +/- 0.9;4.7 +/- 0.8 mmol/l; total ketone bodies -0.2 +/- 0.06; 0.15 +/- 0.05; 0.11 +/- 0.04 mmol/l; lactate - 0.90 +/- 0.33;0.90 +/- 0.24; 1.05 +/- 0.18 mmol/L; alanine - 0.29 +/- 0.06; 0.30 +/- 0.06; 0.31 +/- 0.03 mmol/l. Total ketone body levels were significantly elevated (p less than 0.05) on conventional therapy but not on continuous subcutaneous insulin infusion compared with controls. Variations in metabolites over 24 h, as measured by mean standard deviations, were increased for glucose (p less than 0.001) and for total ketone bodies (p less than 0.05) on the conventional regimes we employed compared with controls. On continuous subcutaneous insulin infusion variations of blood glucose were not affected whereas variations in total ketone bodies were no different from controls. The best possible maternal metabolic control is necessary for normal foetal development and continuous subcutaneous insulin infusion provides a method of achieving this.

Adult↗
PubMed1980

Subcutaneous continuous insulin infusion and control of blood glucose concentration in diabetics in third trimester of pregnancy.

The effect of subcutaneous continuous insulin infusion on the control of blood glucose concentrations was assessed in eight pregnant diabetics in the third trimester. Twenty-four-hour glucose profiles were obtained after strict inpatient control on conventional insulin regimens and after the start of the continuous infusion, which was maintained for 5-55 days. Mean 24-hour glucose concentrations (6.2 mmol/l on conventional regimen, 5.9 mmol/l on continuous infusion; 111.6 and 106.2 mg/100 ml respectively) and mean fasting concentrations (5.3 v 6.2 mmol/l; 95.4 v 111.6 mg/100 ml) were not significantly changed by continuous infusion. Diurnal variations in glucose concentration tended to be smaller on continuous infusion: standard deviation from mean 24-hour glucose concentration was reduced from 2.5 to 2.0 mmol/l (from 45 to 36 mg/100 ml), maximum excursion from 8.4 to 7.4 mmol/l (151.2 to 133.2 mg/100 ml), and M value from 16 to 14. Subcutaneous continuous insulin infusion may be useful in limiting diurnal variations of blood glucose concentrations and warrants further investigation since such an action may be beneficial in the management of pregnant diabetics, in whom the best possible control of blood glucose concentrations is sought for the good of the fetus.

Adult↗
PubMed1980

Peripheral resistance to the cellular action of insulin in obese diabetic subjects in vivo.

1. The concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) in human adipose tissue were studied after intravenous insulin administration (0.3 unit/kg body weight) in obese diabetic and obese non-diabetic subjects. 2. The declines in plasma glucose, glycerol and free fatty acids in the two groups after insulin were similar if allowances were made for the fasting hyperglycaemia in the diabetic subjects. 3. Insulin in vivo lowered the concentrations of cyclic AMP in adipose tissue from non-diabetic subjects. 4. Insulin administration in vivo did not alter the tissue concentrations of cyclic AMP in adipose tissue of obese diabetic subjects. This lack of effect of insulin provides evidence for tissue resistance in vivo to the action of insulin in diabetes mellitus.

Adipose Tissue↗
PubMed1980

Nonaccidental poisoning: the elusive diagnosis.

Although nonaccidental poisoning in childhood is now more often recognised, it is still difficult to establish a diagnosis despite correct investigative procedures. In 1978 we were unable, initially, to establish the cause of intermittent episodes of loss of consciousness in a boy admitted to Sheffield Children's Hospital. Subsequently it was conclusively shown that his mother systematically poisoned him with Tuinal (amylobarbitone and quinalbarbitone) both before admission and while he was being treated in the hospital.

Amobarbital↗