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Biomedical subjects

D Royston

Publications and source records attributed to D Royston.

At least 19 recordsLinked to original sources

Aprotinin does not inhibit the release of PGI2 or vWF from cultured human endothelial cells.

The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human alpha-thrombin, histamine, protamine sulphate, poly-L-lysine and phorbol myristate acetate. Aprotinin (30 microMs) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.

Aprotinin

Aprotinin inhibits platelet adhesion to endothelial cells.

Studies were conducted to assess the effect of the serine protease inhibitor aprotinin on platelet adherence to both thrombin-stimulated and unstimulated human umbilical vein endothelial cells. Aprotinin treatment reduced significantly the adherence of platelets to endothelium pretreated or not with thrombin. In addition, aprotinin similarly reduced the adherence of platelets to plastic or collagen-coated tissue culture wells suggesting that the main site of action of the drug in this system is on the platelets. The role of endothelium-derived relaxing factor (EDRF; nitric oxide) in these platelet-endothelium reactions was investigated by prior incubation of both platelets and endothelial cells with NG-monomethyl-L-arginine (L-NMMA) which prevents the production of nitric oxide. The results demonstrated that nitric oxide was a significant inhibitor of the thrombin-induced platelet adherence in this assay system. Treatment with aprotinin in the presence or absence of L-NMMA reduced adherence of platelets to equivalent levels suggesting that aprotinin acts directly on the platelets via a mechanism that is EDRF-independent, to inhibit adherence.

Aprotinin

Suture technique affects perianastomotic colonic crypt cell production and tumour formation.

Suture line recurrence is an important cause of failure after potentially curative resection for colonic carcinoma. Our aim was to determine whether suture technique affected the incidence of perianastomotic tumours in experimentally induced colonic cancer. Sprague-Dawley rats were randomized into three groups. A 1 cm longitudinal colotomy was repaired with four interrupted 6/0 polypropylene monofilament sutures, using either a transmural technique (n = 18) or a seromuscular technique (n = 18). Control animals (n = 18) had a sham laparotomy. All animals received nine, weekly, subcutaneous injections of azoxymethane (total dose 90 mg/kg) starting 6 weeks after laparotomy. Surviving animals were killed 32 weeks after laparotomy. Five animals from each group were given intraperitoneal bromodeoxyuridine (100 mg/kg) 1 h before being killed. At death, perianastomotic tumours occurred more frequently in animals with transmural sutures than in either controls or those with seromuscular sutures. This difference was associated with a greater mucosal bromodeoxyuridine crypt cell labelling index in the transmural suture group. We conclude that a transmural anastomotic suture technique promotes the development of experimental perianastomotic colonic tumours.

Anastomosis, Surgical

Propofol for long-term sedation in the intensive care unit. A comparison with papaveretum and midazolam.

Thirty-seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit. Fifteen were sedated with a continuous propofol infusion, with analgesia provided by bolus doses of papaveretum. Twelve received a continuous infusion of papaveretum, supplemented by bolus doses of midazolam. The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables. Levels of sedation were generally satisfactory in both groups. Six patients who received propofol required the use of muscle relaxants, because of their strong respiratory drives, to achieve synchronisation with the ventilator. There was no significant difference in respiratory or haemodynamic variables between the groups, but several patients required inotropic support because of their disease. There was no evidence of inhibition of adrenal steroidogenesis in the propofol group. Propofol can be a useful sedative agent in the intensive care unit, but sedative regimens should be tailored to individual patient requirements.

Adolescent

Microprocessor-controlled hemodynamics: a step towards improved efficiency and safety.

Manual titration of sodium nitroprusside (SNP) is widely used for treatment of hypertension following cardiac surgery. This study compared conventional manual control with control by a research prototype of an automatic infusion module based on a proportional plus integral plus derivative (PID) negative feedback loop. Two groups of coronary artery bypass patients requiring SNP for postoperative hypertension were studied prospectively. In the first group, hypertension was controlled by manual adjustment of the SNP infusion rate, and in the second, the infusion rate was controlled automatically. The actual and desired mean arterial pressures (MAP) over consecutive ten-second epochs were recorded during the period of infusion. The MAP was maintained within 10% of the desired MAP 45.8% of the time in the manual group, compared with 90.0% in the automatic group, and the mean percent error in the automatic group was significantly less than in the manual group (P less than 0.01). It is concluded that adoption of such systems will result in improved patient safety and may facilitate more effective distribution of nursing staff within intensive care units.

Analog-Digital Conversion

Major surgery in von Willebrand's disease.

Two patients with von Willebrand's disease underwent major surgery, the first had aortic valve replacement and the second a total hip replacement. Clinically, the best practical test for monitoring the dose of cryoprecipitate necessary to maintain haemostasis was the bleeding time. The response to coagulation factor replacement in von Willebrand's disease is extremely variable, and it is necessary to maintain close coagulation monitoring until the patient's surgical condition is satisfactory for discharge from hospital.

Aged

Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (Trasylol).

The effect of high dose aprotinin (Trasylol) was evaluated in three groups of patients undergoing cardiopulmonary bypass. In a prospective, placebo-controlled, double-blind study, 80 patients having primary aorta-coronary bypass grafting received aprotinin (700 mg approximately) or saline placebo from the beginning of the procedure until skin closure. Standardized anesthetic, perfusion, and surgical techniques were used. The total loss from the thoracic drains was significantly reduced in the aprotinin group as compared with the loss in the placebo group (309 +/- 133 ml versus 573 +/- 166 ml, p less than 0.01; mean +/- standard deviation). There was a threefold difference in the total hemoglobin loss into the chest drains (aprotinin 12.0 +/- 12.6 gm versus placebo 37.7 +/- 18.3 gm). Patients of the aprotinin group received remarkably less bank blood postoperatively: 13 units total compared with 75 units. Of the 40 patients in the aprotinin group, 32 received no bank blood compared with 2 of 37 patients in the placebo group. Venous hemoglobin levels preoperatively, on day 1, and on day 7 postoperatively did not differ between the groups. At day 7 the values were 13.1 +/- 1.4 gm/dl versus 12.5 +/- 1.2 gm/dl in the aprotinin group and the placebo group, respectively. Platelet counts determined at fixed times perioperatively did not differ between the two groups. In contrast, template bleeding time measured in 32 study patients was distinctly different between groups, with a postoperative rise of 6.2 +/- 2.1 minutes in the placebo group opposed to only 1.5 +/- 1.1 minutes in the aprotinin group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin

Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide.

The rate of inactivation of hepatic methionine synthase by nitrous oxide has been determined in 22 patients undergoing laparotomy during general anesthesia, including 70% nitrous oxide. Mean half-time of inactivation was 46 min. Metabolic consequences of nitrous oxide are, thus, critically dependent on the duration of anesthesia, and are unlikely to be significant during exposures of less than 40 min. Inactivation of methionine synthase is very much more rapid in the rat exposed to 50% nitrous oxide, with a half-time of 5.4 min.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran

Free radicals. Formation, function and potential relevance in anaesthesia.

Free radical species are ubiquitous in plant and animal life. This article describes briefly the formation of certain oxygen-centred free radicals which are essential for aerobic metabolism and host defences in humans. The mechanism of cytotoxicity of excess or inappropriate free radical production is described. The potential relevance of free radical tissue injury to the anaesthetist is illustrated using oxygen toxicity, adult respiratory distress syndrome and halothane hepatitis as examples.

Anesthesia

Effect of aprotinin on need for blood transfusion after repeat open-heart surgery.

Of 22 patients undergoing repeat open-heart surgery through a previous median sternotomy wound 11 were randomised to receive the serine proteinase inhibitor aprotinin in high dosage (about 700 mg intravenously from the start of anaesthesia to the end of operation, depending on the length of the surgical procedure). Their mean blood loss was 286 ml compared with 1509 ml in the 11 control patients (p less than 0.001), and mean haemoglobin losses were 8.3 g and 78 g, respectively (p less than 0.001). Blood transfusion requirements were eightfold higher in the control group than in the aprotinin group, 7 of whom received only the single unit of their own blood taken before cardiopulmonary bypass.

Adult

Propofol infusion for sedation in the intensive care unit: preliminary report.

Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.

Blood Pressure