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Biomedical subjects

D Jewitt

Publications and source records attributed to D Jewitt.

At least 19 recordsLinked to original sources
PubMed1998

Chemical processing in the coma as the source of cometary HNC.

The discovery of hydrogen isocyanide (HNC) in comet Hyakutake with an abundance (relative to hydrogen cyanide, HCN) similar to that seen in dense interstellar clouds raised the possibility that these molecules might be surviving interstellar material. The preservation of material from the Sun's parent molecular cloud would provide important constraints on the processes that took place in the protostellar nebula. But another possibility is that HNC is produced by photochemical processes in the coma, which means that its abundance could not be used as a direct constraint on conditions in the early Solar System. Here we show that the HNC/HCN ratio determined for comet Hale-Bopp varied with heliocentric distance in a way that matches the predictions of models of gas-phase chemical production of HNC in the coma, but cannot be explained if the HNC molecules were coming from the comet's nucleus. We conclude that HNC forms mainly by chemical reactions in the coma, and that such reactions need to be considered when attempting to deduce the composition of the nucleus from observations of the coma.

Cyanates↗
PubMed1997

Decrease in factor VII coagulant activity during percutaneous transluminal coronary angioplasty by heparin-mediated lipolytic action.

Levels of factor VII coagulant activity (FVII:C) and two-chain factor VIIa antigen (FVIIa:Ag) were measured in ten patients before and up to 6 h after receiving a bolus of heparin during percutaneous transluminal coronary angioplasty (PTCA). A significant and sustained post-heparin fall in the level of FVII:C was observed (approximately 30%) without any change in the level of FVIIa:Ag. The level of tissue factor antigen within the circulation remained unchanged. The observed decrease in FVII:C coincided with a significant decrease in triglyceride levels presumably due to lipoprotein and hepatic lipase released by the heparin. These findings appear to demonstrate a lipid (triglyceride) dependence of FVII:C. Thus, heparin may act indirectly as antithrombotic agent by limiting a lipid-dependent activation of the extrinsic pathway of coagulation.

Aged↗
PubMed1996

Observations of carbon monoxide in comet Hale-Bopp.

The recently discovered comet Hale-Bopp (C/1995 01) sports a bright dust coma even though it is still far from the sun (presently 6 astronomical units). This feature has attracted considerable interest in the public and scientific arenas. The comet is headed toward perihelion at 0.92 astronomical unit in April 1997 and is widely expected to then become a spectacular naked-eye comet. With millimeter-wave observations, carbon monoxide (CO) has been identified as the driver for the early activity observed in Hale-Bopp.

Carbon Monoxide↗
PubMed1996

Association of antibodies to heat-shock protein-65 with percutaneous transluminal coronary angioplasty and subsequent restenosis.

Heat-shock protein (HSP)-65 of mycobacterial origin has been implicated in the mediation of atherosclerosis by immune mechanisms. Any role of HSP-65 in mediating restenosis is however not clear. We determined the anti-HSP-65 antibodies in 28 patients, 25 male and 3 female, aged 35 to 78 years, with coronary artery disease (CAD) and undergoing percutaneous transluminal coronary angioplasty (PTCA). Of the 28 patients, 12 suffered restenosis five to seven months later. The serum levels of antibody were measured at baseline, immediately after PTCA, before discharge from the hospital, and at 6 weeks, 3 and 6 months after the performance of PTCA. The antibody levels were expressed in OD U/log titre, as explained in the text, and termed estimated OD or EOD. The control group consisted of 29 healthy volunteers, 16 male and 13 female, aged 24 to 59 years. The mean EOD of the patients at baseline was higher than that of the controls (0.60 +/- 0.12, SD; 95% CI 0.56-0.64 compared with 0.53 +/- 0.13; 0.48-0.58; p < 0.01). There were no correlation between age and EOD of patients, controls or both taken together, ruling out the influence of age on the EOD changes in the given age range. The mean antibody levels of the patients with CAD were similar whether or not they suffered subsequent restenosis (0.61 +/- 0.15; 0.53-0.69 in the patency group, and 0.60 +/- 0.10; 0.54-.066 in the restenosis group). However, the patients who did not develop restenosis had a drop in their antibody levels immediately after PTCA (0.51 +/- 0.14; 0.48-0.55; 2-tailed p = 0.029), and at discharge from the hospital (0.52 +/- 0.15; 0.44-0.60; p = 0.036) as compared with the baseline. This decrease of antibodies was not observed in the restenosis group. Furthermore, the anti-HSP-65 antibody levels remained slightly low throughout the 6-month follow-up in the patients with patent coronaries as compared with patients who restenosed, but the decrease was statistically not significant at 5% level at any stage. Besides the anti-HSP-65 antibodies, the levels of anticardiolipin (ACL) antibody were also measured in all the patients. The levels of the ACL antibody were found to be within the normal range before and at all stages after PTCA, ruling out the PTCA-associated change in the anti-HSP-65 antibody as a non-specific occurrence. Thus, a drop in the level of antibody against HSP-65 after PTCA seemed to be associated with a favourable outcome, and may serve as a useful prognostic marker of coronary angioplasty.

Adult↗
PubMed1996

The potential thrombogenic action of a nonionic radiographic contrast medium used during coronary angiography is offset by heparin during coronary angioplasty.

Iohexol sodium, a nonionic radiographic contrast medium, used in invasive imaging techniques has been shown to be potentially thrombogenic. In the present study, the effect of iohexol sodium on haemostatic factors was evaluated in 20 patients, 16 male and 4 female, 10 undergoing coronary angiography and another 10 undergoing coronary angioplasty. All the patients had angiographically-assessed coronary artery disease. The patients undergoing coronary angioplasty received a significantly larger quantity of the dye as compared with the patients undergoing coronary angiography. The former group of patients also received a bolus of 20,000 units of standard heparin in addition. The levels of thrombin-antithrombin-III complex (TAT), prothrombin fragments 1 and 2 (F1F2), D-dimer and the functional activity of tissue factor pathway inhibitor (TFPI) were assayed. While the baseline and 30-min post-dye levels of TAT and F1F2 were comparable in patients undergoing coronary angioplasty, the 30 min levels were significantly elevated in patients undergoing coronary angiography. The post-dye levels of TFPI activity were significantly increased in the former group due to the heparin-induced release of TFPI. It is concluded that the thrombogenic potential of iohexol sodium was overcome by heparin used routinely during coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1993

Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty.

BACKGROUND: Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty. METHODS AND RESULTS: At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 1: bolus, 0.15 mg/kg; infusion, 0.6 mg.kg-1.hr-1 (54 patients); group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg.kg-1.hr-1 (53 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg.kg-1.hr-1 (44 patients); group 4: bolus, 0.45 mg/kg; infusion, 1.8 mg.kg-1.hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg.kg-1.hr-1 (54 patients). The hirulog infusion was maintained for 4 hours; the primary end point was abrupt vessel closure within 24 hours of the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 11.3% compared with 3.9% in groups 4 and 5 (p = 0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT > 300 seconds. CONCLUSIONS: The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure.

Adolescent↗
PubMed1990

A randomized dose-ranging study of rt-PA in acute myocardial infarction. Effects on coronary patency and fibrinolytic parameters.

This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BW rt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7.7 MU), 50 (14.8-29.6 MU) or 100 mg (29.6-48.2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, alpha 2-antiplasmin and fibrin(ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37-69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg-1) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5-86.4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predose fibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. BW rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen.

Aged↗
PubMed1990

Limitations of Doppler ultrasound in the assessment of the function of prosthetic mitral valves.

Pressure half time has been assumed to be a relatively flow-independent measure of orifice area, but it may also be influenced by atrial and ventricular factors. Pressure half time and peak left ventricular inflow velocity were measured by continuous wave Doppler ultrasound in 164 patients with normally functioning Carpentier-Edwards, Björk-Shiley, and Starr-Edwards mitral prostheses. Pressure half time was shorter in the Björk-Shiley than in the other value types and peak transmitral velocity was highest in the Starr-Edwards prostheses. These differences, however, were partly explained by coexistent differences in transmitral flow. Filling time accounted for 19% and stroke volume for 15% of the variance in pressure half time compared with only 5.6% for prosthetic design and 0.4% for annulus diameter when each of these variables was considered alone. The design of the prosthesis explained 18% of the variance in peak transmitral velocity, while cardiac output and annulus diameter did not contribute significantly. With Doppler ultrasound it is impossible to define reliable normal ranges for prosthetic function independently of atrial and ventricular function. Formulas for orifice area based on peak transmitral velocity and flow seem more likely to reflect the behaviour of normally functioning prostheses than those based on pressure half time.

Blood Flow Velocity↗
PubMed1988

Identification of patients at low risk of dying after acute myocardial infarction, by simple clinical and submaximal exercise test criteria.

A consecutive series of 559 hospital survivors of acute myocardial infarction aged less than 66 years were studied; 93 were designated prospectively as low-risk because they were suitable for early submaximal exercise testing and had none of the following clinical or exercise test 'risk factors': (1) angina for at least one month prior to infarction; (2) symptomatic ventricular arrhythmias, or (3) recurrent ischaemic pain, both after the first 24 h of infarction; (4) cardiac failure; (5) cardiomegaly; and (6) an abnormal exercise test (angina, ST-depression or poor blood pressure response). Altogether 301 patients were exercised; their mortality over a median follow-up of 2.4 years was 10.2%, versus 24.6% in the 258 patients not exercised (P = 0.0005). Absence of clinical 'risk factors' alone, in the exercised patients, identified 156 with a mortality of 5.4% versus 15.6% in the 145 with at least one clinical 'risk factor' (P = 0.004). The fully defined low-risk group comprised 93 of the former patients who had neither clinical nor exercise test 'risk factors'. None of these patients died compared with 19 of those with at least one 'risk factor' (mortality = 14.7%; P = 0.002). Their respective rates of non-fatal reinfarction were similar and never exceeded 5% per annum. Therefore, simple clinical and exercise test criteria can positively identify low-risk patients after infarction in whom secondary prevention may be inappropriate.

Adrenergic beta-Antagonists↗
PubMed1987

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.

Aged↗
PubMed1978

Clinical electrophysiological effects of atenolol--a new cardioselective beta-blocking agent.

Atenolol, a cardioselective beta-blocking agent, at dose levels of 0.03, 0.06, and 0.12 mg/kg intravenously, produced prolongation of atrioventricular nodal conduction in 22 patients with suspected coronary artery disease. In a dose of 0.12 mg/kg body weight atenolol produced significant prolongation of sinus cycle length, sinus node recovery time, atrioventricular node conduction, and the effective and functional refractory periods of the atrium and the atrioventricular node. No significant effects were observed on the His Purkinje system or the effective refractory periods of the ventricle. In these actions atenolol closely resembles propranolol. However, because in contrast to propranolol it increases atrial refractoriness, it may have advantages in the treatment of atrial arrhythmias.

Atenolol↗
PubMed1978

Haemodynamic effects of atenolol in patients with coronary artery disease.

The haemodynamic effects of atenolol, a new cardioselective beta-blocking agent, have been studied at rest in 8 patients with coronary artery disease. The drug was administered intravenously in cumulative doses of 0.03, 0.06, and 0.12 mg/kg body weight. A significant decrease in heart rate was associated with a fall in cardiac output. However, this cardiac output fall was not entiely rate dependent, since stroke volume fell significantly both during spontaneous sinus rhythm and when heart rate was maintained constant by atrial pacing. A dose related and significant reduction occurred in left ventricular dP/dt max without significant change in left ventricular filling pressure or mean aortic pressure. Total peripheral resistance at rest rose after atenolol. The haemodynamic findings more closely resemble those which follow intravenous propranolol than those after intravenous practolol in a similar group of patients. These actions of atenolol suggest that it may be a useful agent in the treatment of patients with angina pectoris.

Adult↗
PubMed1978

Contrast media during coronary arteriography: electrocardiographic changes in the presence of normal coronary arteries.

In forty patients with normal coronary arteries, the electrocardiographic changes secondary to Urografin 76 and Hypaque 85 injection into both coronary arteries were monitored. Hypaque caused significantly greater prolongation of the PR interval (p less than 0.001), depression of the ST segment (p less than 0.05) and depth of T wave inversion (p less than 0.05). These effects were more noticeable during right coronary artery injection. Both contrast media slowed the heart rate equally during right and left coronary artery injection. In the absence of coronary arterial disease the ECG changes secondary to contrast media injection probably reflect a direct toxic effect. It is possible that premedication with atropine will reduce these effects. Urografin 76 appears the less toxic of the two media, although one case of ventricular fibrillation occurred with each.

Angiocardiography↗
PubMed1977

Intra-aortic balloon assistance in cardiogenic shock after myocardial infarction or cardiac surgery.

Sixty-eight patients were referred for consideration of intra-aortic balloon assistance, 55 of whom were accepted. Thirty-one patients were in cardiogenic shock after myocardial infarction and the remaining 24 were cardiac surgical patients. Twenty-three of the myocardial infarct group were established on IABA and all 24 of the cardiac surgical patients. Of the 23 patients with cardiogenic shock after myocardial infarction, 19 showed initial haemodynamic improvement on intra-aortic balloon assistance and 5 (22%) survived to leave hospital. Of the 24 cardiac surgical patients, 15 could not be withdrawn from total cardiopulmonary bypass. With intra-aortic balloon assistance, 11 (73%) could be withdrawn from cardiopulmonary bypass and 5 (33%) were hospital and long-term survivors. The remaining 9 surgical patients were in cardiogenic shock in the early postoperative phase, though 5 showed initial haemodynamic improvement there was only one hospital survivor in this group. Intra-aortic balloon assistance was, therefore, of most value in patients dependent on cardiopulmonary bypass. The survival in patients with cardiogenic shock after myocardial infarction was marginally improved.

Assisted Circulation↗
PubMed1977

Indirect measurement of sinoatrial conduction time in patients with sinoatrial disease and in controls.

Clinical recognition of sinoatrial disease currently depends on the presence of transient sinus bradycardia, sinoatrial block, or supraventricular tachyarrhythmias. The value of clinical electrophysiological assessment in these patients is not clear. Using intracardiac electrophysiological recordings and programmed stimulation we have examined 14 patients with sinoatrial disease and 11 control patients undergoing investigation for chest pain. Intracardiac conduction times were normal in all patients. There was no significant difference of sinus node recovery times between the sinoatrial disease and control groups. Sinoatrial conduction times were measured by the indirect method and two populations were identified. However, the mean values of 128 +/- 27 ms in patients and 112 +/- 30 ms in controls were not significantly different and major overlap rendered this measurement clinically valueless. It is concluded that no current electrophysiological measurement has diagnostic value in patients with sinoatrial disease.

Adult↗
PubMed1976

Sustained release procainamide in patients with myocardial infarction.

Sustained release procainamide tablets were administered to 34 patients 48 hours after the onset of an acute myocardial infarct. Therapeutic blood levels of procainamide in the range of 4 to 8 mug/ml were consistently achieved using an 8-hourly maintenance dose of 1.5g after an initial loading dose of 2g. In contrast conventional procainamide capsules administered to 21 comparable patients repeatedly failed to produce plasma concentrations in the therapeutic range, despite the administration of a maintenance dose of 375 mg 3 hourly, after a loading dose of 1g. It is suggested that when the oral administration of procainamide is indicated for the management of ventricular arrhythmias after myocardial infarction, a sustained release preparation should be used.

Delayed-Action Preparations↗
PubMed1976

Cardiac abnormalities in chronic progressive external ophthalmoplegia.

This report describes heart disease in a 32-year-old man with the syndrome of chronic progressive external ophthalmoplegia (CPEO). The surface electrocardiogram showed first degree AV block and left bundle-branch block and there was HV prolongation on the His bundle electrogram. Endomyocardial biopsy showed the changes of hypertrophy on light microscopy, and on electron microscopy there were increased numbers of mitochondria which appeared structurally normal. A permanent demand pacemaker was inserted because these patients are prone to develop complete heart block.

Adult↗