Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 161
Filter
Add more filters

Publication year range
1.
Scott Med J ; 57(2): 99-102, 2012 May.
Article in English | MEDLINE | ID: mdl-22194404

ABSTRACT

The benefits of exercise in the prevention of cardiovascular disease are irrefutable. However, the optimum 'dose' of exercise in order to derive the maximum cardiovascular benefit is not certain. Current national and international guidelines advocate the benefits of moderate-intensity exercise. The relative benefits of vigorous versus moderate-intensity exercise have been studied in large epidemiological studies, addressing coronary heart disease and mortality, as well as smaller randomized clinical trials which assessed effects on cardiovascular risk factors. There is evidence that exercise intensity, rather than duration or frequency, is the most important variable in determining cardioprotection. Applying this evidence into practice must take into account the impact of baseline fitness, compliance and the independent risk associated with a sedentary lifestyle. This review aims to evaluate the role of exercise intensity in the reduction of cardiovascular risk, and answer the question: should you be advising your patients to walk or run?


Subject(s)
Cardiovascular Diseases/prevention & control , Exercise Therapy/methods , Risk Reduction Behavior , Cardiovascular Diseases/physiopathology , Evidence-Based Medicine , Female , Heart Rate , Humans , Male , Oxygen Consumption , Patient Compliance , Physical Endurance , Risk Assessment , Running , Scotland , Walking
2.
Br J Sports Med ; 44(8): 573-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19019900

ABSTRACT

PURPOSE: Physical fitness may confer protection from thrombosis; however, exercise-induced platelet activation may be involved in the triggering of acute vascular events. This study aimed to assess haemostatic responses to acute exercise in trained and sedentary middle-aged subjects. METHODS: 21 first class Scottish football referees and 15 sedentary controls performed a treadmill exercise test. Blood sampling was performed before, immediately after and 30 minutes post-exercise. Samples were analysed for platelet count, prothrombin time, activated partial thromboplastin time (APTT) and serum fibrinogen. Platelet activation was assessed using flow cytometry with CD62 (P-selectin) and antifibrinogen antibodies at rest and in response to ADP and epinephrine. RESULTS: Mean maximal oxygen consumption (Vo2) (ml/kg per minute) achieved was 47.23 (5.02) in the referees and 30.1 (5.2) in sedentary controls. Total platelet count (x10(-9)/l) increased immediately post-exercise (228.2 (40.5), 278.6 (48.9) p=0.001) remaining elevated at 30 minutes in both groups. APTT (s) was reduced immediately post-exercise (32.15 (3.1), 29.7 (3.94) p=0.001) with a further reduction seen at 30 minutes (32.15 (3.1), 28.4 (3.31) p=0.001). In the referees, percentage CD62 expression increased immediately post-exercise (0.688 (0.52), 1.42 (1.3) p=0.008). Percentage antifibrinogen expression increased post-exercise (5.19 (4.31), 13.01 (14.24) p=0.017), with a further increase at 30 minutes (5.19 (4.31), 20.47 (26.8) p=0.02). Similar trends were seen in sedentary controls. CONCLUSION: This study suggests that in an older athletic population, physical fitness does not protect against the prothrombotic effects of exercise. These data suggest that during a football match when referees achieve approximately 80% of peak VO2 (23) they may be at risk of significant platelet activation. Prophylactic platelet inhibition should be considered in this group after appropriate screening and risk stratification.


Subject(s)
Exercise/physiology , Hemostasis/physiology , Soccer/physiology , Adult , Case-Control Studies , E-Selectin/metabolism , Fibrinogen/metabolism , Hemodynamics/physiology , Humans , Oxygen Consumption , Pilot Projects , Scotland
3.
Circulation ; 117(11): 1397-404, 2008 Mar 18.
Article in English | MEDLINE | ID: mdl-18316488

ABSTRACT

BACKGROUND: Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in approximately 80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. METHODS AND RESULTS: Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed > or = 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P=0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (P=0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. CONCLUSIONS: This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.


Subject(s)
Foramen Ovale, Patent/surgery , Heart Septum/surgery , Migraine with Aura/surgery , Prostheses and Implants , Adult , Cardiac Tamponade/etiology , Diagnostic Errors , Double-Blind Method , Endpoint Determination , Female , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/diagnostic imaging , Hemorrhage/etiology , Humans , Male , Middle Aged , Migraine with Aura/etiology , Patient Selection , Pericardial Effusion/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Prostheses and Implants/adverse effects , Retroperitoneal Space , Treatment Failure , Ultrasonography
4.
Science ; 261(5123): 856-63, 1993 Aug 13.
Article in English | MEDLINE | ID: mdl-17783731

ABSTRACT

Massively parallel computers offer scientists a new tool for computation, with capabilities and limitations that are substantially different from those of traditional serial computers. Most categories of large-scale scientific computations have proven remarkably amenable to parallel computation, but often the algorithms involved are different from those used on sequential machines. By surveying a range of examples of parallel scientific computations, this article summarizes our current understanding of the issues of applicability and programming of parallel computers for scientific applications.

5.
Circulation ; 114(18): 1962-7, 2006 Oct 31.
Article in English | MEDLINE | ID: mdl-17062781

ABSTRACT

BACKGROUND: The use of permanent synthetic implants to close atrial septal defects (ASD) and patent foramen ovale (PFO) has a number of limitations, including late complications and the limiting of transeptal access to the left heart should it be required for the later treatment of acquired heart disease. BioSTAR is a novel, bioabsorbable, atrial septal repair implant. This phase I pilot study evaluates the feasibility, safety, and effectiveness of BioSTAR for the first time in humans. METHODS AND RESULTS: We conducted a prospective, open-label, multicenter clinical study in 58 patients aged 28 to 68 years who had a clinically significant ASD or PFO. Percutaneous shunt closure was undertaken with the BioSTAR septal repair implant. Successful device implantation was achieved in 57 (98%) of 58 patients. Closure at 30 days and 6 months, assessed by contrast transthoracic echocardiography, was 48 (92%) of 52 and 54 (96%) of 56, respectively. There was no evidence of a clinically significant response to the device. Transient atrial arrhythmia occurred in 5 patients after implantation. No major safety issues were observed. CONCLUSIONS: This study demonstrates the feasibility, safety, and effectiveness of BioSTAR for the closure of ASD and PFO in humans with a high rate of early and complete shunt closure. BioSTAR is a novel septal repair implant designed to provide biological closure of atrial-level defects using the patient's natural healing response. Because 90% to 95% of the implant is absorbed and replaced with healthy native tissue, future access to the left atrium may be achieved.


Subject(s)
Absorbable Implants , Heart Septal Defects, Atrial/surgery , Adult , Aged , Echocardiography , Feasibility Studies , Female , Heart Septal Defects, Atrial/diagnosis , Heart Septal Defects, Atrial/diagnostic imaging , Humans , Male , Middle Aged , Pilot Projects
6.
Eur J Heart Fail ; 9(4): 429-34, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17126073

ABSTRACT

AIMS: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. METHODS AND RESULTS: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%. The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) -53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P=0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) -0.6(0.2) micromol/L and +0.02(0.2) micromol/L, P=0.02 and iii) creatinine +10.7(3.2) micromol/L and -0.3(2.6) micromol/L, P=0.01. Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: -6 (3) vs. +6 (4); P=0.01. No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. CONCLUSION: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Heart Failure/drug therapy , Mineralocorticoid Receptor Antagonists , Spironolactone/therapeutic use , Aged , Female , Heart Rate , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/drug effects , Quality of Life , Receptors, Mineralocorticoid/drug effects , Severity of Illness Index , Sickness Impact Profile , Stroke Volume
7.
Clin Colorectal Cancer ; 15(2): 186-194.e13, 2016 06.
Article in English | MEDLINE | ID: mdl-27237338

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) testing programs reduce mortality; however, approximately 40% of the recommended population who should undergo CRC testing does not. Early colon cancer detection in patient populations ineligible for testing, such as the elderly or those with significant comorbidities, could have clinical benefit. Despite many attempts to identify individual protein markers of this disease, little progress has been made. Targeted mass spectrometry, using multiple reaction monitoring (MRM) technology, enables the simultaneous assessment of groups of candidates for improved detection performance. MATERIALS AND METHODS: A multiplex assay was developed for 187 candidate marker proteins, using 337 peptides monitored through 674 simultaneously measured MRM transitions in a 30-minute liquid chromatography-mass spectrometry analysis of immunodepleted blood plasma. To evaluate the combined candidate marker performance, the present study used 274 individual patient blood plasma samples, 137 with biopsy-confirmed colorectal cancer and 137 age- and gender-matched controls. Using 2 well-matched platforms running 5 days each week, all 274 samples were analyzed in 52 days. RESULTS: Using one half of the data as a discovery set (69 disease cases and 69 control cases), the elastic net feature selection and random forest classifier assembly were used in cross-validation to identify a 15-transition classifier. The mean training receiver operating characteristic area under the curve was 0.82. After final classifier assembly using the entire discovery set, the 136-sample (68 disease cases and 68 control cases) validation set was evaluated. The validation area under the curve was 0.91. At the point of maximum accuracy (84%), the sensitivity was 87% and the specificity was 81%. CONCLUSION: These results have demonstrated the ability of simultaneous assessment of candidate marker proteins using high-multiplex, targeted-mass spectrometry to identify a subset group of CRC markers with significant and meaningful performance.


Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Mass Spectrometry/methods , Adult , Aged , Area Under Curve , Colorectal Neoplasms/blood , Female , Humans , Male , Middle Aged , ROC Curve , Sensitivity and Specificity
8.
J Clin Endocrinol Metab ; 84(11): 4132-7, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10566661

ABSTRACT

Corticosteroids are important in the regulation of normal physiology and are key factors in regulating cardiovascular physiology and disease, the development of which is known to have a genetic component. However, there is little information on the extent to which plasma and urine steroid levels are determined by familial and genetic factors. We have examined basal and ACTH-stimulated plasma steroid levels and 24-h corticosteroid metabolite excretion rates in 146 pairs of adult twins [75 monozygotic (MZ); 71 dizygotic (DZ)]. Intraclass correlation coefficients were measured for all variables; several plasma steroid measurements were strongly related in both (MZ) and (DZ) twins, consistent with a familial pattern. These included basal levels of 11-deoxycortisol and aldosterone. ACTH-stimulated plasma aldosterone levels were also significantly correlated, to a significant degree, in both MZ and DZ twins. The index of 11beta-hydroxysteroid dehydrogenase activity (tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone) and of the more specific index of activity of the type 2 isoform of this enzyme (urine free cortisol/cortisone) also correlated, to a similar degree, in DZ and MZ twins. In contrast, for the basal and ACTH-stimulated plasma concentrations and 24-h urine excretion rates of several corticosteroids, there was evidence of significant heritability (H2), in that correlation in MZ twins was greater than in DZ. For example, basal plasma corticosterone concentrations (B) (H2 = 0.44), basal and stimulated 11-deoxycorticosterone concentrations (DOC) (H2 = 0.44 and 0.41, respectively), stimulated 11-deoxycortisol concentrations (H2 = 0.53), and the index of 11beta-hydroxylase activity DOC/B (H2 = 0.49) were all significantly heritable. For the urinary variables, 24-h tetrahydrodeoxycortisol (H2 = 0.59) and free aldosterone (H2 = 0.56) were significantly heritable. Our data provide the first evidence that plasma and urine levels of important glucocorticoids and mineralocorticoids show a strong familial pattern, and in some instances, there is evidence of a genetic component to this. This suggests that corticosteroids have a plausible role in essential hypertension that has a similar heritable component.


Subject(s)
Adrenal Cortex Hormones/genetics , 11-beta-Hydroxysteroid Dehydrogenases , Adrenal Cortex Hormones/blood , Adrenal Cortex Hormones/urine , Adrenocorticotropic Hormone , Adult , Aged , Aged, 80 and over , Aldosterone/blood , Aldosterone/urine , Corticosterone/blood , Cortisone/urine , Cortodoxone/analogs & derivatives , Cortodoxone/blood , Cortodoxone/urine , Female , Humans , Hydrocortisone/urine , Hydroxysteroid Dehydrogenases/metabolism , Male , Middle Aged , Twins, Dizygotic , Twins, Monozygotic
9.
Clin Pharmacol Ther ; 66(1): 85-90, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10430113

ABSTRACT

OBJECTIVE: To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D-agonist in patients undergoing cardiac catheterization. METHODS: Ten patients (two men and eight women) without significant obstructive coronary artery disease were administered 3.33 microg/kg/min intravenous eletriptan after they were given a placebo infusion of 0.9% saline solution. Serial measurements of right heart and systemic pressures were taken at 5-minute intervals during placebo infusion, eletriptan infusion, and a 30-minute postinfusion period. Cardiac output by the thermodilution technique and coronary angiography were performed every 15 minutes. Quantitative coronary angiography was carried out to measure coronary artery dimensions. RESULTS: A small but statistically significant increase in occluded wedge pressure (7.4 versus 8.8 mm Hg; 95% confidence interval [CI], 0.74, 2.51; P < .01), right atrial pressure (5.3 versus 6.1 mm Hg; 95% CI, 0.0, 1.4; P < .05), and mean pulmonary artery pressure (13.2 versus 14.6 mm Hg; 95% CI, 0.0, 2.7; P = .05) was observed during the eletriptan infusion compared with placebo. A statistically significant increase in systemic vascular resistance (1256 versus 1519 dyne/sec/cm(-5); 95% CI, 126, 398; P < .01) and pulmonary vascular resistance (76.4 versus 100.8 dyne/sec/cm(-5); 95% CI, 1.9, 46.9; P < .05) was observed in the period after drug infusion. No overall effect was observed on the coronary arteries, although a segmental right coronary artery constriction developed in one patient, possibly as a result of catheter-induced spasm. CONCLUSIONS: Eletriptan, a 5HT1B/1D-agonist effective in migraine, causes no significant coronary artery constriction in patients without significant obstructive coronary artery disease. This finding may reflect a relative selectivity for the 5HT1D-receptor subtype.


Subject(s)
Coronary Vessels/drug effects , Hemodynamics/drug effects , Indoles/pharmacology , Pyrrolidines/pharmacology , Receptors, Serotonin/drug effects , Serotonin Receptor Agonists/pharmacology , Adult , Aged , Female , Humans , Indoles/administration & dosage , Infusions, Intravenous , Male , Middle Aged , Pyrrolidines/administration & dosage , Serotonin Receptor Agonists/administration & dosage , Time Factors , Tryptamines
10.
Atherosclerosis ; 166(1): 137-41, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12482560

ABSTRACT

INTRODUCTION: Although cardiovascular events are known to cluster in families it is unclear the extent to which atherosclerosis per se is genetically determined. The aim of this study was to assess the heritability of carotid intima media thickness (IMT) measurements, a surrogate marker of early atherosclerosis, using a population-based twin study methodology. METHODS: B-mode carotid artery ultrasound images were acquired on 264 twin subjects (142 monozygotic (MZ); mean age 54.3 years and 122 dizygotic (DZ); mean age 51.7 years). An estimate of genetic determination, heritability, was calculated for the IMT parameters before and after correction for confounding variables. RESULTS: An increased carotid IMT was associated with known cardiovascular risk factors (total cholesterol r=0.24, P<0.001 and systolic blood pressure r=0.42, P<0.001) and with a history of coronary events (0.79+/-0.12 vs. 0.72+/-0.14, P=0.01). Carotid IMT measurements demonstrated a familial influence (intra-class correlation of 0.54 for MZ vs. 0.39 for DZ) but no specific genetic determination (heritability estimate 0.31, P=0.15). CONCLUSION: Within a normal population carotid IMT is under a familial, but not genetic influence. The mechanism of genetic control over cardiovascular events may not be mediated through atherosclerotic load as measured by IMT.


Subject(s)
Carotid Artery Diseases/genetics , Carotid Artery, Common/anatomy & histology , Tunica Intima/anatomy & histology , Tunica Media/anatomy & histology , Adult , Aged , Aged, 80 and over , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Carotid Artery, Common/diagnostic imaging , Female , Humans , Male , Middle Aged , Tunica Intima/diagnostic imaging , Tunica Media/diagnostic imaging , Twins, Dizygotic , Twins, Monozygotic , Ultrasonography
11.
Transplantation ; 40(3): 243-9, 1985 Sep.
Article in English | MEDLINE | ID: mdl-2994266

ABSTRACT

The effects of cytomegalovirus (CMV) infection on patient and allograft survival were determined in 1245 renal transplant recipients from 46 transplant centers. When an antilymphocyte preparation was administered to cadaveric allograft recipients, those at risk for primary CMV had a worse outcome than similar patients treated with prednisone and azathioprine (53.1% alive at 6 months with a functioning allograft vs. 70.8%, P = .05) or patients at risk for reactivation CMV (53.1% vs. 71.1%, P = .035). Patients at risk for reactivation CMV had a better outcome if they received an antilymphocyte preparation (71.1% vs. 60.8%, P less than .01). The type of immunosuppression had no effect on patients without CMV. Living-related donor transplantation was not significantly influenced by CMV or type of immunosuppression. We conclude that CMV infection is strongly influenced by the form of immunosuppression employed, and that both are important determinants of the outcome of cadaveric renal transplantation.


Subject(s)
Cytomegalovirus Infections/immunology , Kidney Transplantation , Age Factors , Antibodies, Viral/analysis , Blood Transfusion , Cytomegalovirus/immunology , Cytomegalovirus Infections/complications , Diabetes Complications , Graft Survival , Histocompatibility Antigens/analysis , Humans , Immunosuppression Therapy
12.
Am J Cardiol ; 80(5A): 51E-54E, 1997 Sep 04.
Article in English | MEDLINE | ID: mdl-9296471

ABSTRACT

A "look-and-act" approach, using a strategy of early intervention, and a "watchful waiting" approach, using medical therapy, are compared for the management of patients with unstable coronary artery disease (UCAD). Results from clinical trials are used to illustrate the advantages of antiplatelet and antithrombotic therapy and the problems associated with early intervention. Finally, a clinical management strategy for patients with UCAD is outlined. It is concluded that watchful waiting appears to be the most effective way of managing both patients and resources.


Subject(s)
Coronary Disease/therapy , Angina, Unstable/drug therapy , Angina, Unstable/surgery , Angina, Unstable/therapy , Angioplasty, Balloon, Coronary , Coronary Disease/drug therapy , Coronary Disease/surgery , Humans , Myocardial Infarction/drug therapy , Myocardial Infarction/surgery , Myocardial Infarction/therapy , Randomized Controlled Trials as Topic , Thrombolytic Therapy , Time Factors , Treatment Outcome
13.
Am J Cardiol ; 80(5A): 30E-34E, 1997 Sep 04.
Article in English | MEDLINE | ID: mdl-9296467

ABSTRACT

The safety and efficacy of weight-adjusted, low-molecular-weight heparin (dalteparin) was compared with that of unfractionated heparin during 6 days of treatment in 1,482 patients with unstable angina or non-Q-wave myocardial infarction. Dalteparin, at a lower dose, was compared with placebo during the following 39 days. No significant outcome difference was found between the 2 treatment regimens in the unblinded phase (days 1-6). Between days 6-45 the rates of death, myocardial infarction, and recurrence of angina were comparable between the active treatment and placebo groups. The results suggest that twice-daily administration of subcutaneous dalteparin may be an effective and safe alternative to unfractionated heparin during the acute phase of unstable coronary artery disease. Prolonged treatment with dalteparin at a lower once-daily dose did not confer any additional benefit over aspirin (75-165 mg) alone.


Subject(s)
Angina, Unstable/drug therapy , Anticoagulants/therapeutic use , Dalteparin/therapeutic use , Myocardial Infarction/drug therapy , Angina, Unstable/mortality , Anticoagulants/administration & dosage , Dalteparin/administration & dosage , Humans , Injections, Subcutaneous , Myocardial Infarction/mortality , Prospective Studies , Survival Analysis , Treatment Outcome
14.
Am J Cardiol ; 60(4): 231-7, 1987 Aug 01.
Article in English | MEDLINE | ID: mdl-3113222

ABSTRACT

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.


Subject(s)
Myocardial Infarction/drug therapy , Recombinant Proteins/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Clinical Trials as Topic , Coronary Angiography , Double-Blind Method , Electrocardiography , Humans , Infusions, Intravenous , Myocardial Infarction/diagnostic imaging , Random Allocation , Recurrence , Time Factors , Tissue Plasminogen Activator/administration & dosage , Vascular Patency
15.
Br J Pharmacol ; 68(3): 373-9, 1980 Mar.
Article in English | MEDLINE | ID: mdl-7052333

ABSTRACT

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.


Subject(s)
Acebutolol/pharmacology , Coronary Disease/physiopathology , Heart/drug effects , Hemodynamics/drug effects , Propranolol/pharmacology , Animals , Coronary Circulation/drug effects , Dogs , Myocardial Contraction/drug effects
16.
Br J Pharmacol ; 51(1): 15-9, 1974 May.
Article in English | MEDLINE | ID: mdl-4155334

ABSTRACT

1 The effects of tolamolol on haemodynamics and myocardial contractility were investigated in two groups of six patients undergoing diagnostic cardiac catheterization.2 The intravenous administration of tolamolol (0.15 mg/kg) produced a significant fall in heart rate from a control value (87 +/- 7 to 62 +/- 3 beats/min) 5 min after administration and a concomitant fall in cardiac output from 4.7 +/- 0.9 to 3.5 +/- 0.8 litres/minute. There was no significant change in systemic blood pressure, pulmonary artery blood pressure or stroke volume.3 There was no change in left ventricular end diastolic pressure after tolamolol. There was a fall in the maximum rate of rise of the left ventricular pressure (LV dp/dt(max)) and the derived index of the left ventricular contractile state (V(max)).4 These results suggest that tolamolol has a predominantly negative chronotropic but also a lesser negative inotropic action on the heart.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Heart/physiology , Hemodynamics/drug effects , Propanolamines/pharmacology , Adrenergic beta-Antagonists/administration & dosage , Adult , Benzamides/administration & dosage , Benzamides/pharmacology , Blood Pressure/drug effects , Cardiac Catheterization , Cardiac Output/drug effects , Cresols/administration & dosage , Cresols/pharmacology , Heart Diseases/physiopathology , Heart Function Tests , Heart Rate/drug effects , Humans , Injections, Intravenous , Middle Aged , Propanolamines/administration & dosage
17.
Drugs ; 29 Suppl 2: 76-80, 1985.
Article in English | MEDLINE | ID: mdl-3987554

ABSTRACT

Oral felodipine (10mg) was given to 11 patients undergoing routine invasive electrophysiological studies. Systolic blood pressure fell by 31 mm Hg from 130 +/- 17.5 to 99 +/- 10 mm Hg (mean +/- SD, p less than 0.001) while diastolic pressure fell from 78 +/- 9 to 60 +/- 8mm Hg (p less than 0.001), thus confirming its vasodilator properties. Heart increased from 64 +/- 10 to 78 +/- 16 beats/min (p less than 0.001). The A-H interval was significantly prolonged from 97 +/- 14 to 110 +/- 24 msec (p less than 0.01) while there was no change in the H-V interval. Sinus node recovery time showed no change when corrected for heart rate. The effective refractory period of the atrioventricular node was shortened from 317 +/- 38 to 287 +/- 27 msec (p less than 0.01) as was the effective refractory period of the ventricular Purkinje fibres from 251 +/- 18 to 237 +/- 20 msec (p less than 0.005). These haemodynamic and electrophysiological changes suggest that this compound is an effective vasodilator and may have potential antiarrhythmic properties.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Arrhythmias, Cardiac/physiopathology , Nifedipine/analogs & derivatives , Adult , Aged , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Electrophysiology , Felodipine , Female , Heart Conduction System/drug effects , Heart Rate/drug effects , Humans , Male , Middle Aged , Nifedipine/pharmacology , Sinoatrial Node/drug effects
18.
Drugs ; 33 Suppl 3: 117-23, 1987.
Article in English | MEDLINE | ID: mdl-3315576

ABSTRACT

Anisoylated plasminogen streptokinase activator complex (APSAC) is a recently developed thrombolytic agent with high fibrin-binding potential and sustained release pharmacokinetics (plasma half-life 70 minutes). Following studies of its intracoronary use, the efficacy was examined, in an open study using coronary angiography, of a single bolus dose of 30U given intravenously to 94 patients within 6 hours (mean 2.97 hours) from the onset of symptoms of myocardial infarction. After thrombolytic therapy, patency of the left anterior descending artery was demonstrated in 32 of 42 patients with anterior infarctions (76%), and in 12 of 13 patients with circumflex (92%) and 28 of 36 with right coronary artery infarcts (78%) in the inferior infarction group. The overall incidence of reocclusion was 24%, which occurred within the first 12 days after hospitalisation. Successful thrombolysis was associated with rapid resolution of the acute ST segment change, and an early peak of creatine phosphokinase (CK) compared with patients whose vessels remained occluded. No major systemic bleeding complications were experienced. Single dose intravenous APSAC appears to be a highly effective and relatively safe thrombolytic agent which has the major advantage over other such agents of easier administration. This makes it suitable for use in district hospitals and in the community, as well as in specialised cardiac centres.


Subject(s)
Fibrinolytic Agents/therapeutic use , Myocardial Infarction/drug therapy , Plasminogen/therapeutic use , Streptokinase/therapeutic use , Vascular Patency/drug effects , Adult , Aged , Anistreplase , Electrocardiography , Female , Humans , Injections, Intravenous , Male , Middle Aged
19.
Drugs ; 29 Suppl 2: 81-6, 1985.
Article in English | MEDLINE | ID: mdl-3987555

ABSTRACT

The combined use of some beta-adrenoceptor blocking agents with calcium channel blockers may cause adverse pharmacodynamic drug interactions: hypotension, heart block or even asystole may be precipitated. The electrophysiological effects of combined administration of intravenous metoprolol 10mg and the vasodilating calcium antagonist felodipine (0.1 mg/kg/bodyweight) were assessed in an open study by invasive methods. Following metoprolol, the heart rate was reduced from 69 +/- 24 to 60 +/- 16 beats/min (mean +/- SD, p less than 0.05) with a minor prolongation of the sinus node recovery time. The A-H interval was increased from 94 +/- 25 to 109 +/- 16 msec (p less than 0.005) and the H-V interval was unchanged. The effective refractory period of the atrioventricular node was prolonged from 327 +/- 54 to 361 +/- 62 msec (p less than 0.01) with a minor prolongation of the effective refractory period of the ventricular Purkinje fibres. Systolic and diastolic blood pressures showed a mean reduction of 11 (p less than 0.001) and 6mm Hg (p less than 0.05), respectively. Following felodipine, the changes in heart rate and effective refractory periods of the atrioventricular node and ventricular Purkinje fibres returned towards control values. No further prolongation of the A-H interval resulted and further blood pressure changes were minor. The absence of adverse haemodynamic or electrophysiological effects suggests that this combination of agents may be safely used.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Metoprolol/pharmacology , Nifedipine/analogs & derivatives , Vasodilator Agents/pharmacology , Adult , Aged , Anti-Arrhythmia Agents/administration & dosage , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Arrhythmias, Cardiac/physiopathology , Blood Pressure/drug effects , Drug Synergism , Electrocardiography , Electrophysiology , Felodipine , Female , Heart Conduction System/drug effects , Heart Rate/drug effects , Humans , Male , Metoprolol/administration & dosage , Middle Aged , Nifedipine/administration & dosage , Nifedipine/pharmacology , Purkinje Fibers/drug effects , Vasodilator Agents/administration & dosage
20.
Am J Clin Pathol ; 72(3): 473-8, 1979 Sep.
Article in English | MEDLINE | ID: mdl-112857

ABSTRACT

Cryptosporidia are sporozoan parasites that infect epithelial cells of the gastrointestinal tract. Infection with cryptosporidia has been found most commonly in a variety of animal species and only rarely in man. The authors report a case of an immunosuppressed renal-transplant recipient with IgA deficiency who experienced diarrhea and fever and was found to have cryptosporidia in a jejunal biopsy specimen and in air-dried smears of the specimen. By electron microscopy, trophozoite, schizont, and macrogamete forms were identified, and these forms ahd morphologic features similar to those of cryptosporidia previously found in guinea pigs. Treatment of the cryptosporidial infection in this case was with trisulfapyrimidines. The efficacy of this treatment could not be evaluated because of complications.


Subject(s)
Coccidiosis/complications , Immunoglobulin A , Immunologic Deficiency Syndromes/complications , Kidney Transplantation , Apicomplexa/ultrastructure , Humans , Jejunum/parasitology , Male , Middle Aged , Transplantation, Homologous
SELECTION OF CITATIONS
SEARCH DETAIL