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Biomedical subjects

D Royston

Publications and source records attributed to D Royston.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of aprotinin on vascular reactivity of coronary bypass grafts.

OBJECTIVE: Aprotinin reduces postoperative bleeding and the need for transfusion after cardiopulmonary bypass. The current clinical concern about aprotinin is that it may increase the incidence of postoperative graft thrombosis and thromboembolic phenomena. The fact that the mechanism of action of aprotinin is not completely elucidated and that its effects on the vascular reactivity of bypass conduits are unknown raise doubts regarding its safety. In an attempt to clarify these issues we investigated the vascular reactivity of the human saphenous vein and internal thoracic artery to a range of vasoconstrictor agents in the presence or absence of aprotinin. METHODS: Human saphenous vein was obtained from 24 patients and internal thoracic artery from 7 patients undergoing coronary artery bypass. Vessels were set up in organ baths to record changes in vessel wall tension. RESULTS: Endothelium-dependent relaxations to acetylcholine in saphenous vein rings were unaffected after aprotinin treatment. Contractions to the thromboxane analog U46619 were significantly attenuated after aprotinin treatment in the saphenous vein. Maximum responses were reduced from control values of 88 +/- 7.5 mN to 49.3 +/- 4.8 mN with 1 mumol/L doses of aprotinin (p < 0.05) and 36.6 +/- 4.8 mN with 10 mumol/L doses of 5-hyroxytryptamine or noradrenaline after aprotinin incubations. Furthermore, contractions to U46619 in the internal thoracic artery were unaffected by aprotinin. CONCLUSION: Our data show that there is a preservation of endothelium-dependent responses to acetylcholine and a reduced U46619 vasoconstrictor action on the saphenous vein after aprotinin treatment. Thus the direct effect of aprotinin on the vessel wall could counteract the potential effect of its prothrombotic action on graft patency.

Acetylcholine↗
PubMed1997

The inflammatory response and extracorporeal circulation.

Defining the cause of organ and tissue dysfunction associated with the use of perfusion systems will produce methods of prevention or treatment and improve patient outcome. The problem is the plethora of triggers, effectors, and mediators in this process, which can now be measured. Each new measureable compound becomes another biochemical "smoking gun" without physiological data to show any relevance to the human problem. This review critically compares and contrasts the role of certain, largely novel, initiation, amplification, and cytotoxic mechanisms in the inflammatory response of the myocardium and pulmonary systems after a period of cardiopulmonary bypass. The available evidence strongly points to the process being different for each of these tissue beds. These data suggest that ensuring normal lung and heart functions after surgery will require separate therapeutic strategies.

Blood Proteins↗
PubMed1997

Effect of temperature and cardiopulmonary bypass on the pharmacokinetics of remifentanil.

Sixteen patients undergoing coronary revascularization requiring cardiopulmonary bypass received remifentanil 2 micrograms kg-1 or 5 micrograms kg-1 by infusion over 1 min after sternotomy but before commencing cardiopulmonary bypass, during hypothermic cardiopulmonary bypass and during cardiopulmonary bypass after rewarming. Hypothermic cardiopulmonary bypass reduced the clearance of remifentanil by an average of 20%, and this was attributed to the effect of temperature on blood and tissue esterase activity. Reductions in arterial pressure occurred with administration of both doses during normothermia only.

Adolescent↗
PubMed1997

Clinics in diagnostic imaging (28).

A 44-year-old man presented with sudden headache and neck stiffness. Computed tomography (CT) demonstrated subarachnoid haemorrhage. CT and magnetic resonance (MR) angiography showed the cause to be a ruptured anterior communicating artery aneurysm. These findings were confirmed by digital subtraction angiogram and at surgery. The role of imaging in detection of cerebral aneurysms is briefly discussed.

Adult↗
PubMed1997

Noncirrhotic hepatoma presenting with paraneoplastic neurologic manifestations: two cases.

Hepatocellular carcinoma usually occurs in patients with cirrhosis and is rarely associated with paraneoplastic neurologic disorders. We describe two young patients with hepatomas occurring in noncirrhotic livers, both of whom presented with neurologic symptoms. A 19-yr-old man who presented with coma and a 23-yr-old woman with a 3-month history of progressive hemiparesis, dysarthria, and altered affect were each found, at autopsy, to have hepatocellular carcinoma occurring in a noncirrhotic liver. Neuropathologic examinations revealed widespread multifocal necrotizing leukoencephalopathy in the man and occlusive noninflammatory cerebral vasculopathy with widespread cortical and subcortical infarcts in the woman. It is unlikely that the neuropathologic findings in these patients are explicable on the basis of antibody-mediated tissue injury.

Adult↗
PubMed1996

Preventing the inflammatory response to open-heart surgery: the role of aprotinin and other protease inhibitors.

This review discusses the role of protease inhibition in reducing or preventing certain of the deleterious effects of major surgery. The ability of agents such as aprotinin to inhibit bleeding and reduce the need for donor blood transfusions is now well established. What is less well recognized is that aprotinin is not simply an antifibrinolytic but is a polyvalent enzyme inhibitor of many of the enzymes which are involved in inflammatory and hemostatic processes. Inappropriate activation of these pathways is considered to be important in the genesis of the inflammatory response to open-heart surgery. The first part of the article reviews aspects of the inflammatory and hemostatic systems which have a common basis and which utilize proteolytic actions for their control. In the later part of the review, the effect of a period of cardiopulmonary bypass on organ and tissues is discussed together with the effects of protease inhibition to prevent any abnormal or inappropriate response to the stimulus. Consideration of these aspects will hopefully allow a more rational and scientific approach to the uses, possible benefits and perceived or real safety issues following administration of these agents.

Animals↗
PubMed1996

Serine protease inhibition prevents both cellular and humoral responses to cardiopulmonary bypass.

Serine proteases are ubiquitous and are fundamentally responsible for many of the control processes in plasma. Hemostasis and inflammation have the same evolutionary origins and developed as host-defense mechanisms. This article highlights this development and defines the role of serine proteases in the complex inflammation and coagulation cascades that have evolved to maintain homeostasis. Generation of the serine protease thrombin plays a pivotal role in the regulation of many functions and is able to initiate activation and release of a number of humoral mediators involved in the inflammatory and hemostatic systems. Control processes are required to limit coagulation and inflammation to sites of injury, and a number of these have at their center inhibitors of serine proteases (SERPIN). A vast number of inhibitors are found throughout nature. In addition to these naturally occurring SERPINs, a number of others are available for administration to both animals and humans. Of these, aprotinin is a complex polypeptide; there are other chlormethyl ketones and small synthetic agents that also act as potent SERPINs. A second group of compounds are not protein inhibitors but have a broad spectrum of inhibition, e.g., a gabexate mesylate (FOY) and nefamostat (FUTHAN). The profound actions of aprotinin, FUTHAN, and FOY to inhibit bleeding and prevent the need for donor blood are well known. The potential role of these agents, particularly aprotinin, to reduce the inflammatory effects of cardiac and other kinds of surgery is considered. The data on SERPINs actions to reduce neutrophil-induced tissue injury are reviewed, with particular reference to the inflammatory events that occur during surgery with cardiopulmonary bypass.

Antibody Formation↗
PubMed1995

Distribution, morphology, and neurochemistry of endocardial and epicardial nerve terminal arborizations in the human heart.

BACKGROUND: The heart contains a variety of morphologically distinct nerve terminals known to influence cardiac function. Little is known about the distribution, morphology, and neurochemistry of these terminals in the human heart. METHODS AND RESULTS: We examined the entire endocardial and epicardial surfaces of infant and adult hearts obtained postmortem and at transplantation using immunohistochemical and histochemical staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diameter, 6 to 10 microns) immunoreactive for myelin basic protein were identified in the atrial endocardium, epicardium, and coronary sinus, and four types were distinguished by differences in immunostained nerve area (range, 358 to 797 microns 2) and dispersion (range, 620 to 4684 microns 2). These terminals displayed immunoreactivity for tyrosine hydroxylase, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in < 5% of endocardial terminals and in no epicardial terminals arising from myelinated fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be associated with local ganglia. A distinct population of terminals (mean stained area, 35 microns 2; 18 to 53 microns 2, 95% CI; and mean dispersion, 59 microns 2; 38 to 80 microns 2, 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 microns; 2.2 to 2.8 microns, 95% CI) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. CONCLUSIONS: Specialized nerve terminals are distributed more widely in the human heart than has been described in experimental animals. These terminals express either AChE activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity, suggesting that acetylcholine, catecholamines, and neuropeptide Y may be present in sensory and autonomic nerves in the human heart.

Acetylcholinesterase↗
PubMed1995

Pancreatic vipomas: spectrum of presentation and evolution of diagnostic and therapeutic modalities.

Two patients are reported who presented with symptoms characteristic of a pancreatic vipoma. The necessity to measure more than one plasma VIP level for diagnosis, and the delay between the onset of illness and diagnosis is illustrated by both cases. Evidence suggests that vipomas are still under reported. The evolution of sophisticated diagnostic and therapeutic modalities over the twenty-five years separating both presentations is discussed.

Combined Modality Therapy↗
PubMed1995

Aprotinin in patients having coronary artery bypass graft surgery.

Any therapy must have a benefit and a risk. The benefit of aprotinin therapy in reducing bleeding is well known. Data presented over the past 12 months have confirmed this efficacy and the superiority and consistency of aprotinin therapy in direct comparison with other pharmacologic (desmopressin, tranexamic acid) and physical (administration of fresh platelet concentrate) interventions. The debate has now changed to focus on issues of the safety of this agent. In particular, concerns have been expressed as to the effect of this agent on renal function, thrombotic potential (and thus graft patency), and adverse reactions on a second exposure. Most recent reports show plasma creatinine concentrations are higher in treated than in nontreated patients on the 3rd or 4th postoperative day. The concentrations reached were not outside the clinical range, and there were no clinical sequelae of this biochemical abnormality. Focused studies have shown no effect of the use of aprotinin therapy on early graft patency or the incidence of thromboembolic complications. The reporting of hypersensitivity reactions following aprotinin administration suggests that the incidence is not different to other agents used in open heart surgery. Three reports of fatal or near-fatal cardiovascular collapse associated with the use of aprotinin followed the apparently inappropriate administration of the agent.

Aprotinin↗