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Biomedical subjects

J Hosking

Publications and source records attributed to J Hosking.

6 recordsLinked to original sources

The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis.

BACKGROUND AND OBJECTIVES: Intermittent pneumatic compression (IPC) is an effective form of deep vein thrombosis prophylaxis for general surgery patients. The antithrombotic effect of IPC is thought to be the result of increased venous velocity and stimulation of endogenous fibrinolysis. However, the mechanism of enhanced fibrinolytic activity and the relative effects on normal and postthrombotic veins have not been defined. The purposes of this study are 1) to quantify changes in fibrinolytic activity with IPC; 2) to study the mechanism of fibrinolytic enhancement with IPC; and 3) to evaluate whether postthrombotic patients have the same capacity for fibrinolytic enhancement with IPC as do normal subjects. METHODS: Twelve volunteers (6 normal and 6 postthrombotic) had 5 IPC devices applied for 120 minutes in random fashion, 1 per week x 5 weeks. The devices included single-chamber, sequential, foot, calf, and long-leg compression. Subjects had an indwelling antecubital venous cannula placed for blood drawn at baseline, 60, 120, and 180 minutes after IPC devices were applied. Global fibrinolytic activity (euglobulin fraction, fibrin plate assay), tissue plasminogen activator (tPA) antigen (Ag) and activity (Act), plasminogen activator inhibitor-1 (PAI-1) Ag and Act, alpha-2-antiplasmin-plasmin complexes, and von Willebrand factor (vWF) antigen were assayed. RESULTS: A striking elevation in fibrinolytic activity was noted at 180 minutes with all devices in normal subjects and postthrombotic patients (p = 0.01-0.0001); however, baseline and stimulated fibrinolytic activity was attenuated in postthrombotic patients (<0.03). The tPA-Act increased only in normal subjects (3.8 +/- 1.9%) (p = 0.057), despite a decrease in plasma tPA-Ag, which was observed in both normal subjects (-12.4 +/- 3.8%) (p = 0.009) and patients (-17.2 +/- 3.1%) (p = 0.001). PAI-1-Ag decreased in both normal subjects (-13.4 +/- 3.8%) (p = 0.007) and patients (-12.0 +/- 3.1%) (p = 0.013) with a marked reduction in PAI-1-Act in both normal subjects (p = 0.003) and patients (p = 0.004). There were no changes in vWF, and alpha-2-antiplasmin-plasmin complexes increased only in postthrombotic patients (p = 0.021). CONCLUSIONS: Stimulation of endogenous fibrinolytic activity occurs after IPC, both in normal subjects and postthrombotic patients; however, baseline and overall fibrinolytic response in postthrombotic patients is reduced. The mechanism of increased fibrinolytic activity is likely because of a reduction in PAI-1, with a resulting increase of tPA activity.

Adult↗

The effects of hypercholesterolaemia, simvastatin and dietary fat on the low density lipoprotein receptor of unstimulated mononuclear cells.

The in vivo expression and regulation of the LDL receptor of circulating mononuclear cells was studied using a sensitive spectrophotometric assay with low density lipoproteins conjugated to colloidal gold (LDL-gold). The high plasma cholesterol of familial hypercholesterolemic subjects was shown to be related to a low in vivo LDL receptor activity; cells from a homozygote had virtually no activity and those from 24 heterozygotes expressed 45% of the activity of cells from 35 normals. The average receptor activity of cells from 18 polygenic hypercholesterolemic (PH) subjects was not significantly different from normal but a low expression may have been a factor in six of these subjects. Simvastatin increased the LDL receptor activity of cells from the PH subjects by 70% while lowering their plasma cholesterol by 26%, but reducing the fat intake from 38% to 20% of energy and cholesterol from 239 to 96 mg/day had no effect on the receptor despite a 10% reduction in plasma cholesterol. Upregulation of the LDL receptor may therefore have been involved in the lowering of plasma cholesterol by simvastatin but not by the reduction in dietary fat and cholesterol.

Anticholesteremic Agents↗

A biochemical study on mothers of children with congenital neurodevelopmental abnormalities.

A biochemical study has been undertaken on the mothers of children with a major neurodevelopmental disability, without known etiology (study group), and an appropriate control group. Two hundred seventy-four mothers were studied, 137 in each group. Social and environmental details were recorded in each of the two major groups. Biochemical studies included the assay of plasma and urinary amino acids and appropriate screening tests for carbohydrate and organic acid abnormalities. To introduce an element of standardization and also to enhance the opportunities for identifying possible biochemical heterozygote states, a 50-g protein mean was given to all subjects approximately three-quarters of an hour before blood and urine samples were taken. Difference of means tests on 22 amino acids revealed 9 significant t values at the 0.05 level and all means were significantly lower in the study groups. Because of the differences noted a discriminant analysis was carried out which demonstrated an extremely high proportion of correctly classified subjects (98%) when biochemical parameters were used to attempt to classify subjects into the study or control group.

Amino Acids↗

Patient-controlled postoperative analgesia with alfentanil. Adaptive, on-demand intravenous alfentanil or pethidine compared double-blind for postoperative pain.

A double-blind study comparing alfentanil and pethidine given intravenously by an adaptive, patient-controlled on-demand analgesic system is described. It was demonstrated that, despite its well-known rapid onset of effect, alfentanil took several hours to achieve good quality analgesia. Nevertheless, it had a much more predictable consumption pattern than pethidine. Alfentanil was associated with significantly less sedation during the postoperative period than pethidine, and was also associated with a significantly greater urine output during the 24-hour period of study. There was no evidence of tolerance or accumulation with either of the two drugs.

Adult↗