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Biomedical subjects

S J McDonald

Publications and source records attributed to S J McDonald.

At least 19 recordsLinked to original sources
PubMed1999

Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis.

The PFA-100 device is a new instrument for the in-vitro testing of platelet function. Primary haemostasis is stimulated by recording the closure time taken for platelets to seal a 150 microm aperture in the centre of a membrane coated with collagen and either epinephrine or ADP. Patients with type 3 von Willebrand's disease (n = 4) all had infinitely prolonged closure times (> 200 s) with both types of cartridge. A patient with afibrinogenemia exhibited only slightly prolonged closure times of 111 and 166 s for the ADP and epinephrine membranes, respectively. Patients with Glanzmann's thrombasthenia (n = 6) and Bernard Soulier syndrome (n = 2) had grossly prolonged closure times (> 200 s) with both types of cartridges. These results confirmed that the PFA-100 system was highly dependent on normal von Willebrand factor, glycoprotein Ib and glycoprotein IIb/IIIa levels but not on plasma fibrinogen. Patients with storage pool disease (n = 6) and Hermansky Pudlak syndrome (n = 7) had prolonged closure times with the epinephrine cartridge. There was no evidence of enhanced platelet function in patients with antiphospholipid syndrome, in sickle-cell disease or thalassemia. However, ingestion of aspirin resulted in a near consistent and significant prolongation of the closure time for the epinephrine cartridge but not for the ADP cartridge in both normal subjects and patients. The test offers a reliable, reproducible, rapid and simple means of assessing high-shear platelet function in vitro.

Blood Platelets↗
PubMed1998

Prothrombin time derived fibrinogen determination on Sysmex CA-6000.

AIM: To evaluate PT derived fibrinogen determinations with reference to the Clauss fibrinogen assay using a Sysmex CA-6000 random access coagulation analyser. METHODS: Samples were analysed from normal subjects (n = 20), patients with renal or liver dysfunction (n = 25), critically ill patients (n = 25), patients receiving oral anticoagulant treatment (n = 50), and patients with a haemoglobinopathy (n = 127). Prothrombin times were performed using two thromboplastins: one derived from rabbit brain (Dade: Thromboplastin IS) and the other from recombinant human tissue factor (Dade: Innovin). Fibrinogen was assayed by the Clauss method using a commercial kit (Dade: Fibrinogen). RESULTS: The relation between Clauss fibrinogen and PT derived fibrinogen was found to be dependent on the patient's clinical group and source of the thromboplastin used. When the data from the above sample groups were pooled there was still a significant difference (p < 0.001) between Clauss fibrinogen and PT derived fibrinogen, irrespective of thromboplastin used. CONCLUSIONS: It is unsafe to use the PT derived fibrinogen for patient monitoring owing to non-uniform variability in response to clinical status and reagent employed; however, it may prove to be a useful screening test in a research environment for estimating fibrinogen levels among defined patient groups.

Animals↗
PubMed1997

Relationship between preoperative endotoxin immune status, gut perfusion, and outcome from cardiac valve replacement surgery.

STUDY OBJECTIVE: Endotoxin is a powerful trigger of systemic inflammation. Since cardiac surgery exposes patients to endotoxemia, this study was set up to define the relationship between preoperative endogenous endotoxin immune status, gut perfusion, and outcome following cardiac valve replacement surgery. DESIGN: Observational study. SETTING: University hospital. PATIENTS: Fifty-nine consecutive patients undergoing cardiac valve replacement. MEASUREMENTS AND MAIN RESULTS: Blood was assayed for IgG and IgM endotoxin core antibody (EndoCAb) levels preoperatively, immediately postoperatively, and at 4 h and 24 h postoperatively. Intraoperative gut mucosal perfusion was assessed using gastric tonometry. Complications were assessed for groups above and below the median EndoCAb value of a healthy population (100 median units micro/mL). Of the 59 patients, 12 developed at least one of a set of predefined complications. Of these 12, all had preoperative levels of IgM EndoCAb below 100 MU/mL (p<0.025). Eleven had IgG EndoCAb levels below 100 MU/mL (0.05<p<0.1). There was no relationship between the fall in gastric intramucosal pH and exposure to endotoxin as implied by the fall in unbound IgM EndoCAb levels, although the specificity of tonometry for predicting complications could be improved by considering the patient's preoperative EndoCAb status. CONCLUSIONS: Preoperative EndoCAb levels were related to poor outcome following cardiac surgery and may be used to improve the specificity of GI tonometry in predicting postoperative complications.

Adolescent↗
PubMed1993

Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

OBJECTIVE: To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. DESIGN: Double blind, randomised controlled trial. SETTING: Two metropolitan teaching hospitals in Perth, Western Australia. SUBJECTS: All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. MAIN OUTCOME MEASURES: Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. RESULTS: 3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. CONCLUSIONS: There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted.

Blood Pressure↗
PubMed1993

Importance of pharmacokinetic and physicochemical data in the discovery and development of novel anti-arrhythmic drugs.

1. The importance of pharmacokinetics and physicochemical data in the discovery and development of a new mono-cationic antiarrhythmic agent, bidisomide (pKa 9.3), structurally related to the di-cationic anti-arrhythmic disobutamide (pKa of 8.6 and 10.2) and a mono-cationic drug disopyramide (pKa 10.4), is described. 2. In man, the di-cationic disobutamide was slowly eliminated with a mean terminal phase half-life of 54 +/- 18 h, a value > 7 times longer than disopyramide. The long terminal phase half-life of disobutamide is attributed to high accumulation of the drug in the tissues, a phenomenon attributed to the di-cationic nature. 3. Structural modification of disobutamide resulted in the mono-cationic agent bidisomide, designed to minimize drug accumulation in the tissues. Human studies with bidisomide confirmed that the terminal phase elimination of this drug was much faster than that of disobutamide, with a half-life of about 11h. The absolute bioavailability of bidisomide was 45-62% which is lower than that of disopyramide (60-90%). 4. Unlike disopyramide, absorption of bidisomide was complex, characterized by a lag period (0.75-1.5 h) before absorption, followed by occurrence of two peaks in the plasma concentration-time curves. 5. The characteristic double peaks found with bidisomide was attributed to two rapid absorption sites of the drug in the gastrointestinal tract.

Adolescent↗
PubMed1992

Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Administration, Oral↗
PubMed1991

Constructed-response matching to sample and spelling instruction.

The development of interactive programmed instruction using a microcomputer as a teaching machine is described. The program applied a constructed-response matching-to-sample procedure to computer-assisted spelling instruction and review. On each trial, subjects were presented with a sample stimulus and a choice pool consisting of 10 individual letters. In initial training, sample stimuli were arrays of letters, and subjects were taught to construct identical arrays by touching the matching letters in the choice pool. After generalized constructed-response identity matching was established, pictures (line drawings) of common objects were presented as samples. At first, correct spelling was prompted by also presenting the printed name to be "copied" via identity matching; then the prompts were faded out. The program was implemented with 2 mentally retarded individuals. Assessment trials determined appropriate words for training. Correct spelling was established via the prompt-fading procedure; training trials were interspersed among baseline trials that reviewed and maintained spelling of previously learned words. As new words were learned, they were added to a cumulative baseline to generate an individualized review and practice battery for each subject.

Adult↗
PubMed1990

Simple in vitro method to characterize antiarrhythmic agents.

A simple, nonmicroelectrode method was developed for the in vitro identification and characterization of potential antiarrhythmic agents. To evaluate the method, standard antiarrhythmic agents from three different classifications (I, III, IV) were tested in isolated right ventricular guinea pig papillary muscles for their effect on developed tension (DT), excitability (EX), and effective refractory period (ERP). ERP was measured with the use of paired field stimuli. Depression or reversal of the force frequency relationship was an index of an agent's effect on DT. A shift in the stimulus strength-duration relationship was an index of an agent's effect on EX. A computer program was developed for data handling and analysis. Disopyramide phosphate (D, 3.0 x 10(-5) M), sotalol (S, 3.0 x 10(-5) M), clofilium phosphate (C, 1.0 x 10(-5) M), and N-acetyl procainamide hydrochloride (N, 3.0 x 10(-5) M) significantly prolonged ERP (+20, +35, +24, +16 ms, respectively), while verapamil (V, 3.0 x 10(-7) M) and the distilled water vehicle (W) did not. D and V significantly decreased DT (-78% and -57% at 1 Hz, respectively) while W, S, C, and N did not. Only D decreased EX. These data correspond well with findings in other models reported in the literature, supporting the use of this simple in vitro method for identification and characterization of potential antiarrhythmic agents.

Acecainide↗
PubMed1989

Cardiovascular profile of a new anti-arrhythmic agent, SC-40230.

The cardiac and general haemodynamic effects of SC-40230, a newly developed anti-arrhythmic agent with both class 1a and 1b properties, were assessed in two different types of experiments using anaesthetised dogs, and in experiments using isolated cat papillary muscles. At the canine anti-arrhythmic dose (9 mg.kg-1 intravenously), SC-40230 decreased the maximum rate of rise of the left ventricular pressure (LV dP/dtmax) by 20%. It decreased heart rate slightly, and lowered (greater than 10%) blood pressure only at doses greater than the canine anti-arrhythmic dose. In these experiments there were dose dependent increases in the P-R interval and the QRS duration. In isolated cat papillary muscles, SC-40230 had a weak negative inotropic effect (IC20 = 3.3 X 10(-5) mol.litre-1) which was less than that previously reported for disopyramide phosphate (IC20 = 1.8 X 10(-5) mol.litre-1) or mexiletine (IC20 = 2.1 X 10(-5) mol.litre-1). These findings suggest SC-40230 has a minimal cardiovascular and haemodynamic side effect potential in its anti-arrhythmic dose range. If these results are confirmed in clinical studies, SC-40230 may have an improved side effect profile versus other anti-arrhythmic drugs such as disopyramide.

Animals↗
PubMed1988

SC-36602, a new antiarrhythmic agent: comparison of its cardiovascular profile with that of other antiarrhythmic drugs.

The cardiovascular profile of SC-36602, a new class 1A/1B antiarrhythmic agent, was compared to those of disopyramide, lidocaine, mexiletine, flecainide, encainide, lorcainide, and quinidine. These drugs were compared at their respective canine antiarrhythmic doses in a hemodynamic evaluation using anesthetized dogs. In another test using anesthetized dogs, the cardiovascular effects of cumulative doses of SC-36602 were assessed. The direct negative inotropic potential of each drug was also determined using isolated cat papillary muscles. In the hemodynamic study, SC-36602 and quinidine did not cause significant myocardial depression, measured as a decrease in the maximal first derivative of the left ventricular pressure. (Heart rate and diastolic filling pressure were not controlled in order to mimic clinical conditions). SC-36602, mexiletine, flecainide, and quinidine increased heart rate. SC-36602 and mexiletine caused a small increase in mean arterial pressure, whereas disopyramide and quinidine decreased it. Disopyramide was the only drug studied that increased left ventricular end-diastolic pressure. SC-36602, quinidine, and mexiletine increased index of cardiac effort. Disopyramide caused a decrease in the latter. Disopyramide, flecainide, encainide, and lorcainide lengthened the ECG intervals. Cumulative intravenous doses of SC-36602 up to 50 mg/kg produced significant decreases in mean arterial pressure, increases in heart rate, and increases in P-R and QRS intervals of the ECG relative to placebo-matched controls. SC-36602 had the least direct negative inotropic action of the drugs studied, as measured in isolated papillary muscles. These data suggest SC-36602, when compared to the other antiarrhythmic drugs studied, has the least amount of hemodynamic side-effects at its antiarrhythmic dose.

Animals↗
PubMed1983

Toxic shock syndrome complicated by laryngeal oedema.

A 50-year-old woman was admitted as an acute medical emergency and was diagnosed as having toxic shock syndrome. Thirty-six hours after admission she went into hepato-renal failure and had disseminated intravascular coagulation. She developed severe laryngeal oedema, a complication which has not been reported previously, and was intubated with great difficulty. She recovered from this, but died 5 weeks after the presentation of a pulmonary embolus.

Female↗