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Biomedical subjects

J B Leslie

Publications and source records attributed to J B Leslie.

At least 19 recordsLinked to original sources
PubMed2001

How can we best prevent or treat postoperative nausea and vomiting?

In pursuit of preventing or rapidly rescuing patients from postoperative nausea and vomiting, new clinical studies provide revised postoperative nausea and vomiting risk prediction tools, risk stratification formulae, comparative trials to identify the most appropriate cost-effective anti-emetics, and several trials recommending the addition of steroids in anti-emetic prophylactic multimodal approaches. Common variables that identify high-risk postoperative nausea and vomiting patients include female sex, a history of postoperative nausea and vomiting or motion sickness, young age, volatile anesthetic agents, nitrous oxide, and the administration of opioids. The most successful approach to the prevention of postoperative nausea and vomiting is multimodal, with combination anti-emetics, dexamethasone, aggressive hydration, the avoidance of opioids, and aggressive pain control.

Journal Article↗
PubMed1997

The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery.

UNLABELLED: Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis. We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg x kg(-1) x h(-1) infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting. IMPLICATIONS: In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting.

Aminocaproic Acid↗
PubMed1994

Characterization of prothrombin activation during cardiac surgery by hemostatic molecular markers.

BACKGROUND: Prothrombin activation represents the key regulatory step in the hemostatic process. Once formed, thrombin contributes to the generation of fibrin as well as the activation of platelets and fibrinolysis. Failure to suppress thrombin formation during cardiac surgery could result in disorders of hemostasis and thrombosis in the perioperative period. The aim of this study was to determine the time course for prothrombin activation during the perioperative period associated with cardiac surgery. METHODS: We measured prothrombin activation during the perioperative period in 19 adult patients undergoing primary cardiac surgery using enzyme-linked immunosorbent assays for the detection of thrombin formation (prothrombin fragment 1.2 and thrombin-antithrombin III complex) and thrombin activity (fibrinopeptide A and fibrin monomer). Blood samples were obtained preoperatively; at 30-min intervals during cardiopulmonary bypass (CPB); and 1, 3, and 20 h after completion of CPB. RESULTS: Despite anticoagulation with heparin, plasma concentrations of prothrombin fragment 1.2, thrombin-antithrombin III complex, and fibrin monomer increased throughout CPB. Peak concentrations for all hemostatic markers occurred in the samples obtained 3 h after completion of CPB. By the morning after surgery, plasma prothrombin fragment 1.2 returned to preoperative concentrations; however, fibrinopeptide A and fibrin monomer concentrations remained significantly increased (P < 0.05) compared to preoperative values. CONCLUSIONS: These data clearly demonstrate the occurrence of prothrombin activation and thrombin activity during CPB despite heparin concentrations adequate to maintain the activated clotting time greater than 400 s. Hemostatic markers for the activation of prothrombin demonstrated peak concentrations 3 h after completion of CPB with a return to baseline concentrations by the morning after surgery. Markers for thrombin activity, however, suggest the presence of active thrombin through the morning after surgery. Further investigations will be necessary to determine the role of hemostatic activation in thrombotic complications after cardiac surgery.

Aged↗
PubMed1993

Incidence and aetiology of perioperative hypertension.

The reported incidence of perioperative hypertension associated with coronary artery bypass-graft (CABG) surgery ranges from 30-80%, which may reflect the various definitions of the condition as well as differences in the patients' preoperative states. Systolic, diastolic and mean arterial blood pressures are variously used to define perioperative hypertension, but absolute values range from a target systolic blood pressure of below 170 mmHg in some studies to below 110 mmHg in others. Patients' preoperative states have been extensively studied to determine potential risk factors. The majority of these studies indicate that perioperative hypertension is predictive of perioperative cardiac morbidity, but others do not confirm this finding, rendering the issue unresolved. The consequences of perioperative hypertensive episodes include bleeding from vascular suture lines, cerebrovascular haemorrhage or subendocardial ischaemia, and are associated with a mortality rate that may approach 50%. Increases in peripheral vascular resistance (PVR), caused by elevated levels of circulating catecholamines, appear to be the primary aetiology. Antihypertensive agents which correct or prevent the increase in PVR would appear to be the most appropriate therapy. However, no single agent appears to be ideal for all hypertensive episodes, suggesting multiple potential aetiologies.

Cardiac Surgical Procedures↗
PubMed1993

Haemodynamics and tissue specificity with isradipine.

The significant effects of isradipine in producing arterial vasodilation and mild negative chronotropic effects without significant negative inotropic effects suggests that this agent should provide excellent antihypertensive efficacy in the treatment of perioperative hypertension. Isradipine may prove to be a safe antihypertensive treatment in patients with impaired ventricular function (cardiac failure), impaired myocardial perfusion (ischaemia), and in cases of selected conduction abnormalities or arrhythmias. The demonstration that its effects are limited to vascular resistance rather than vascular capacitance is an important distinguishing feature of isradipine compared with other antihypertensive agents. Finally, the potential application of this dihydropyridine calcium antagonist for cytoprotection and its effects on atherosclerosis remain exciting therapeutic prospects.

Hemodynamics↗
PubMed1990

Labetalol for the control of elevated blood pressure following coronary artery bypass grafting.

In a multicenter study, the efficacy and safety of intravenous (IV) labetalol for the control of elevated blood pressure were studied in the intensive care unit (ICU) in 65 patients within 4 hours following coronary artery bypass grafting (CABG). Patients with pre-existing ventricular dysfunction, bradycardia, bronchospastic disease, or postoperative complications were excluded. All patients were monitored with a thermodilution pulmonary artery catheter. Entry criteria were a systolic blood pressure (SBP) greater than 140 mm Hg or diastolic blood pressure (DBP) greater than 90 mm Hg for at least five minutes. Intravenous labetalol was loaded incrementally (5, 10, 20, and 40 mg at 10-minute intervals) to a maximum cumulative dose of 75 mg, until either SBP decreased 10% or DBP decreased 10% and was less than 90 mm Hg. Responders were entered into a 6-hour maintenance period, and received 5 to 40 mg of IV labetalol every 10 minutes as needed for blood pressure control. Hemodynamic data and temperature were recorded at baseline, just before each dose of labetalol during the loading period, and at the end of the maintenance period. Alternative therapy was given in the case of nonresponse or adverse events. Intravenous labetalol successfully controlled post-CABG hypertension in 55 of 65 patients (85%); of these, 46 responded to 35 mg or less. Although 28 patients required no further labetalol in the maintenance period, in the others dosage varied from 5 to 400 mg. Reductions in SBP and DBP were associated with moderate reductions in pulse pressure (SBP-DBP) and heart rate (HR). Cardiac index decreased by 18.5%, with a 12.5% decrease in stroke index and 8.1% decrease in HR. Systemic vascular resistance did not increase significantly. Four patients (6%) developed hypotension related to IV labetalol. There was one death due to perioperative myocardial infarction, which was unrelated to labetalol use. The mechanism of action of IV labetalol in controlling hypertension after CABG surgery seems to be moderate negative inotropy and chronotropy. Its alpha-blocking effects seem to be important in preventing reflex vasoconstriction. This is directly opposite to the primary vasodilator effect found when IV labetalol is used to control nonsurgical hypertension. Because of these actions, labetalol should be avoided or used with caution in patients with preoperative and postoperative cardiac dysfunction. In patients with normal left ventricular function, IV labetalol appears to be a safe, effective agent in controlling post-CABG hypertension, with the added potential benefit of enhanced myocardial oxygen balance.

Analysis of Variance↗
PubMed1989

Attenuation of the hemodynamic responses to endotracheal intubation with preinduction intravenous labetalol.

Endotracheal intubation following anesthesia induction frequently produces hypertension and tachycardia. This study evaluated the efficacy of preinduction IV labetalol for attenuating the hemodynamic responses to intubation following thiopental and succinylcholine induction of anesthesia. Two hours after diazepam (10 mg by mouth), 60 patients were randomized in a double-blind manner and received IV saline or labetalol at doses of 0.25, 0.5, 0.75, or 1 mg/kg in a parallel design study. Five minutes later, thiopental (4 mg/kg) and succinylcholine (1 mg/kg) were administered, and the trachea was intubated in 2 minutes. Nitrous oxide (70%) anesthesia was maintained for 10 minutes. Hemodynamic parameters were grouped and analyzed for significance (p less than 0.05) by two-way repeated measures analysis of variance and t-test with Bonferroni adjustments. Baseline group demographics and hemodynamics were comparable. All doses of labetalol significantly attenuated the rate-pressure product increase immediately postintubation versus placebo. There was a dose-dependent attenuation of the increases in heart rate and the systolic, diastolic, and mean blood pressures versus placebo following intubation. IV labetalol at doses up to 0.75 mg/kg offers an effective pharmacologic means of attenuating preoperative hemodynamic responses to endotracheal intubation.

Adult↗
PubMed1988

Atrial natriuretic peptide plasma levels during cardiac surgery.

In this investigation, the hypothesis was tested that patients with valvular heart disease have higher atrial natriuretic peptide (ANP) plasma levels than patients with coronary artery disease during cardiac surgery. Six patients scheduled for valve replacement (group V) and seven scheduled for coronary artery bypass grafting (CABG) (group C) were studied. ANP plasma levels and hemodynamic measurements were obtained at several times during surgery. ANP levels were elevated in both groups compared to those measured in healthy volunteers; and ANP levels in valvular patients were found to be higher than in the CABG patients. In addition, isotonic fluid loading, rewarming during cardiopulmonary bypass, and weaning from cardiopulmonary bypass increased ANP from baseline in group C. Mean arterial pressure and ANP levels correlated in group C. Ejection fraction, pulmonary artery diastolic pressure, and right atrial pressure did not correlate with ANP levels in either group. In conclusion, patients with valvular heart disease have higher ANP levels during surgery compared to patients with coronary artery disease. This difference probably relates to different pressure and volume loads on atrial tissue.

Aged↗
PubMed1987

Continuous intrathecal opioid analgesia: tolerance and cross-tolerance of mu and delta spinal opioid receptors.

The tolerance effects of continuous intrathecal infusions of opioids at mu and delta receptors were studied in rats. These effects were compared to those of chronic systemic morphine. A chronic intrathecal infusion of the relatively selective delta agonist, [D-Ala2, D-Leu5]enkephalin (DADLE), produced a larger degree of tolerance to DADLE than to the highly specific mu-activating morphiceptin analog [N-methyl-Phe3, D-Pro4]morphiceptin (PL017). The slope of the analgesic dose-response curve for the highly specific delta agonist, cyclic [D-Penicillamine2, D-Penicillamine5]enkephalin (DPDPE), was significantly different (flatter) from those of mu agonists or DADLE. High-dose infusion of PL017 induced a 61-fold parallel shift of the dose-response curve for PL017. This same treatment also induced a corresponding flattened, nonparallel change of the dose-response curve for DADLE. This altered curve for DADLE was very similar in slope to that of DPDPE. Pretreatment with the irreversible mu antagonist, beta-funaltrexamine, caused a parallel rightward shift of the dose-response curve for PL017 but did not affect DPDPE activity. beta-Funaltrexamine treatment induced a nonparallel rightward shift of the dose-response curve for DADLE with a change of slope similar to that of DPDPE. These findings demonstrate a mixed mu-delta analgesic activity for the compound DADLE, which is often referred to as a prototypic delta agonist. These interactions differ from prior reports of none or minimal mu-ligand interactions with DADLE. Despite the cross-reactivity of DADLE to mu receptors, DADLE remains a more effective analgesic than do mu agonists in states of mu receptor tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1986

Interaction between highly selective mu and delta opioids in vivo at the rat spinal cord.

Possible interactions between mu- and delta-receptors in the rat spinal cord were studied using the radiant-heat-induced tail flick response and the highly selective mu- or delta-ligands: [NMePhe3,D-Pro4] morphiceptin(PL-17) and cyclic[D-Pen2,D-Pen5]enkephalin(DPDPE). Intrathecal infusions of PL-17 (0.5 microgram/hr) for 5 days caused 61- and 6-fold shifts to the right of the dose-response curves for PL-17 and DPDPE, respectively. Since PL-17 and DPDPE are highly selective agonists for mu- and delta-receptors, the partial cross-tolerance to the delta-agonist induced by PL-17 is probably not resultant from a cross-reactivity between these ligands. These data suggest that there may be an interaction between mu- and delta-receptors in the rat spinal cord.

Analgesics↗
PubMed1985

Eicosanoids in the central nervous system.

All mammalian tissue investigated to date is capable of eicosanoid biosynthesis in response to various activating stimuli. While the importance of these metabolites as major mediators of many normal physiological processes and some pathophysiological conditions has not been proven, it is evident that these compounds are at least important modulators of many cellular and organ system functions. This review is intended to provide the reader with a brief overview of eicosanoid biology, with specific reference to the neurosciences. The increasing knowledge about the role of the eicosanoids in neurobiology may contribute to the understanding and treatment of many neurological diseases. The eicosanoids comprise several groups of biologically active unsaturated fatty acids: the "primary" prostaglandins, the cyclic endoperoxides, the prostanoids, the leukotrienes, and other acid lipids. This article includes a review of the enzymatic pathways of biosynthesis and metabolism of eicosanoids in man, and the pertinent structural nomenclature. The general basic and clinical pharmacological effects of the more important compounds on vascular perfusion, platelet function, intracellular enzyme activity, and interactions with other mediators of cellular activity are reviewed. A more detailed review of the actions of eicosanoids as mediators or modifiers of central nervous system physiology and pathophysiology is presented. Recent animal and human studies on the use and alterations of the eicosanoid metabolites is summarized, specifically where they relate to several clinical problem areas of interest to the neurosurgeon and neurobiologist. These areas include cerebrovascular circulation physiology, cerebral ischemia, cerebral vasospasm following subarachnoid hemorrhage, migraine headaches, hypothalamic function, neurotransmission, and nociception. A bibliography of 92 articles for further review is also included.

Central Nervous System↗
PubMed1977

Regulation of function of transplanted parathyroid glands in man.

The results of studies performed in nine patients who had undergone successful parathyroidectomy and gland transplantation are presented. Transplantation of parathyroid tissue to the forearm, performed for therapeutic reasons, provided a unique opportunity to sample parathyroid gland effluent and to assess secretory function in vivo. The relationship of calcium to immunoreactive parathyroid hormone (iPTH) release was studied during calcium and ethylenediamine tetraacetic acid (EDTA) infusions as well as dialysis against a low calcium bath (low calcium dialysis) in patients with chronic renal failure. Calcium infusions caused an abrupt decrease in hormone release down to a persistent base line within 30 minutes, whereas EDTA infusion caused a sharp increase which peaked between 30 to 60 minutes and returned towards base line despite continuation of the hypocalcemic stimulus. Low calcium dialysis caused an irregular release of hormone which appeared to deplete gland reserves during the period of the stimulus. Ready access to the venous effluent of the transplanted tissue makes this an excellent model for studying parathyroid physiology in man.

Calcium↗