A new antibody capture enzyme linked immunoassay specific for transforming growth factor beta 1.

Previous studies which examined Transforming Growth Factor beta 1 (TGF-beta 1) generation have relied on the identification of TGF-beta 1 mRNA or measurement of TGF-beta 1 by bioassay. Quantitation of TGF-beta 1 message alone however is inadequate since the regulation of TGF-beta 1 synthesis is often post-transcriptional. TGF-beta 1 is poorly immunogenic, and sensitive and specific immunoassays for this peptide have proved difficult to develop. Bioassays depend on stimulation or inhibition of cell proliferation in a TGF-beta 1 dependent manner, and are very rigid in their requirements for optimal performance. The aims of this work was therefore to develop a sensitive and reproducible immunoassay for TGF-beta 1. Microtitre plates were coated with human recombinant TGF-beta 1, unbound protein was discarded from the wells prior to blocking with bovine serum albumin. Chicken anti-human TGF-beta 1 antibody was incubated with the test solution overnight at 4 degrees C and then added to the coated wells. Bound antibody was detected with alkaline phosphatase conjugated anti-chicken antibody. The assay is sensitive to 0.2 ng/ml with a range to 100 ng/ml. The assay detects the mature form of human recombinant TGF-beta 1, natural platelet extracted TGF-beta 1, and TGF-beta 1 derived from human monocytes stimulated with Phorbol myristate acetate (PMA). Active TGF-beta 1 is measured directly and latent TGF-beta 1 can be measured indirectly following acid activation of samples. Inter-assay precision ranged from 4.3 to 9.6%, (coefficient of variation, %CV) and intraassay precision ranged from 2.8 to 8.6% (CV).(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation.

In a randomized, double-blind, controlled study of 98 patients with atrial fibrillation (AF) (present for > or = 30 minutes, < or = 72 hours, and a ventricular response of > or = 100 beats/min), intravenous flecainide (2 mg/kg, maximum 150 mg) was compared with intravenous amiodarone (7 mg/kg) and placebo. Exclusion criteria included significant left ventricular dysfunction, inotrope dependence, recent antiarrhythmic therapy, hypokalemia, and pacemaker dependence. Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect. Twenty of 34 patients (59%) given flecainide, 11 of 32 (34%) given amiodarone, and 7 of 32 (22%) given placebo reverted to stable sinus rhythm in < or = 2 hours after starting medication (chi-square 9.87, p = 0.007). More patients reverted to stable rhythm with flecainide than with placebo (p = 0.005; odds ratio 5.1, 95% confidence interval 1.54 to 17.5). There was no significant difference between amiodarone and placebo or between flecainide and amiodarone. However, after 8 hours there were no significant differences in reversion between the treatment groups: flecainide (n = 23, 68%), amiodarone (n = 19, 59%), and placebo (n = 18, 56%). Amiodarone promptly reduced the ventricular rate, and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful: flecainide was no more effective than placebo in controlling ventricular rate. Adverse effects were not significantly different in the 3 groups. Thus, intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo. Amiodarone, although less effective in reverting AF, slows the rapid ventricular response.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide.

Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi-square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of flecainide for the reversion of acute onset atrial fibrillation.

The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double-blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9-24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment of a secondary prevention program for coronary bypass patients.

To treat atherosclerosis systemically in the surgical patient, proper drug therapy and risk factor modification are necessary. A secondary prevention program for coronary bypass patients was established at the University of North Carolina School of Medicine for that purpose. Modifiable risk factors, such as hypercholesterolemia and hypertension, are identified preoperatively, and therapy is initiated postoperatively, with follow-up in the Risk Reduction Clinic at 3 and 6 months. Treatment is designed to achieve defined goals in secondary prevention.

Cardiac pacing in intensive care.

Cardiac pacing techniques and equipment have developed dramatically in recent years. Bradycardias and tachycardias may be effectively treated by pacing. Bradyarrhythmias: It is generally accepted that pacing is indicated for a sustained symptomatic bradycardia. Prophylactic pacing for 'high-risk' bundle branch block in acute myocardial infarction is more controversial. A new era in cardiology has been introduced with the advent of 'physiological pacing', i.e. pacing of the heart with the maintenance of atrioventricular synchrony and varying the heart rate according to the body's metabolic leads. Modern pacing systems, which allow the atria and ventricles to contract in sequence, improve cardiac haemodynamics, result in subjective improvement and increase exercise tolerance. There are, however, pacemaker-associated and pacemaker-mediated tachyarrhythmias. Further advances in technology should overcome these problems. Tachyarrhythmias: Intracardiac electrocardiograms are often useful in the diagnosis of tachyarrhythmias, especially wide complex tachycardias. Rapid pacing of the atria in certain supraventricular tachycardias or of the ventricle in ventricular tachycardia is an alternative to cardioversion in many instances. This form of treatment is usually utilised in conjunction with drug therapy.

Indications for and complications of temporary transvenous cardiac pacing.

A prospective survey was conducted of the indications for and complications of 153 temporary transvenous cardiac pacing lead insertions in 148 patients. Pacing for bradyarrhythmias or potential bradyarrhythmias (Group I) accounted for 105 insertions, wide complex tachycardia (Group II) 17, and narrow complex tachycardia (Group III) 31 pacing electrode insertions respectively. The infraclavicular subclavian vein approach was used in 73%. The median insertion time was 20 minutes. Group I: 77% were undertaken because of severe symptoms. On 64 occasions (61%) the patient had complete heart block or ventricular asystole. Group II: The lead was inserted to treat and often assist in the diagnosis of the wide complex tachycardia. Ventricular 'burst' pacing reverted ventricular tachycardia in 13 (76%). Group III: Rapid atrial 'burst' pacing was used to treat supraventricular tachyarrhythmias (paroxysmal supraventricular tachycardia and atrial flutter) resistant to medical therapy. Pacing was successful in reverting 28 (90%). A complication occurred in 27 (18%) of 153 lead insertions, 11 (7%) were serious. No complication resulted in the death of a patient. Temporary transvenous pacing is safe and effective for the treatment of bradyarrhythmias and certain tachyarrhythmias.

Echocardiography in intensive care: the basics. Part I.

OBJECTIVE: To review the current status of echocardiography in critically ill patients with special reference to the advantages and disadvantages of the transthoracic and transoesophageal approaches. DATA SOURCES: A review of articles published in peer reviewed journals from 1976-1999 and identified through a MEDLINE search on echocardiography. SUMMARY OF REVIEW: Echocardiography uses the reflection of high frequency sound waves at tissue boundaries to construct a two-dimensional image of cardiac structures. Two-dimensional echo-cardiography is the cornerstone of cardiac ultrasound, although Doppler techniques (pulsed wave, continuous wave, and colour flow) form an integral part of every modern echocardiographic study. The Doppler effect is based on changes in sound frequency that occur when a sound source moves towards or away from an observer. Blood flow velocities measured by Doppler can be used to estimate pressure, valve area and stroke volume. The standard imaging positions of the probe are either outside the thorax (i.e. transthoraracic echocardiography or TTE) or inside the oesophagus (i.e. transoesophageal echo-cardiography or TOE) both of which provide information that can be helpful in managing critically ill patients. CONCLUSIONS: Echocardiography is a rapidly developing technology. Cardiac structures can be imaged in 'real time'. Image quality continues to improve. The use of transoesophageal probe positioning has also widened the potential of this bedside technique in critically ill patients.

Echocardiography in Intensive Care: The Basics. Part II.

OBJECTIVE: To review the current status of echocardiography in critically ill patients with special reference to the advantages and disadvantages of the transthoracic and transoesophageal approaches. DATA SOURCES: A review of articles published in peer reviewed journals from 1976-1999 and identified through a MEDLINE search on echocardiography. SUMMARY OF REVIEW: Echocardiography is a rapidly evolving field which is relatively new to intensivists. Both transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) are extremely useful in managing critically ill patients. In intensive care practice echocardiograpy is used to evaluate clinical syndromes such as unexplained hypotension, search for source of sepsis or source of emboli, as well as haemodynamic assessment and monitoring. TOE although somewhat invasive, provides superb images which often assist in both diagnosis and improved treatment. CONCLUSIONS: Echocardiography often provides useful information in critically ill patients. Intensivists should familiarise themselves with this new technology and if possible become skilled practitioners of this exciting technique. The care of critically ill patients will benefit from its widespread use.

Comparative therapeutic efficacy of clinafloxacin in a pneumococcal meningitis mouse model.

The therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, was compared with that of ciprofloxacin and ceftriaxone in a novel pneumococcal meningitis mouse model. Mice were challenged by the intracerebral ventricular route with 50 IL of a lethal bacterial suspension and treated subcutaneously 2 h later. Both penicillin-susceptible and multidrug-resistant pneumococcal strains were used for evaluation. Survival percentages were calculated as the median curative dose (CD50) using log-probit statistical methods. Ceftriaxone was the most active agent against the penicillin-susceptible strain (CD50 = 2 mg/kg), but showed a 30-fold decrease in potency against the resistant strain. Clinafloxacin was equally effective against both strains, and proved to be the most active agent against the penicillin-resistant pneumococcus.

Hemodynamic benefit of maintaining atrioventricular synchrony during cardiac pacing in critically ill patients.

OBJECTIVE: To determine the hemodynamic effects of maintaining atrioventricular synchrony during emergency cardiac pacing in critically ill patients. DESIGN: Prospective, within patient double-blind study. SETTING: ICU or coronary care unit patients in a university hospital. PATIENTS: Forty (23 cardiac surgery, ten acute myocardial infarction, and seven general intensive care) seriously ill patients with severe symptomatic bradycardia. INTERVENTION: Initial randomization of patients to receive either a pacing mode where atrioventricular synchronization was maintained (atrioventricular pacing: atrial demand, atrioventricular sequential, atrioventricular universal) or a mode of pacing where atrioventricular synchrony was not preserved (ventricular demand pacing). MEASUREMENTS AND MAIN RESULTS: The cardiac output increased from a mean of 4.5 +/- 1.7 L/min (95% confidence intervals: 4.0 to 5.0 L/min) during ventricular demand pacing to 5.3 +/- 1.7 L/min (95% confidence intervals: 4.9 to 5.9 L/min) during atrioventricular pacing (p less than .0001) despite trivial decreases in CVP from 14 +/- 4 mm Hg (95% confidence intervals: 13 to 15 mm Hg) to 13 +/- 5 mm Hg (95% confidence intervals: 12 to 15 mm Hg) and pulmonary artery occlusion pressure from 18 +/- 5 mm Hg (95% confidence intervals: 16 to 20 mm Hg) to 17 +/- 5 mm Hg (95% confidence intervals: 15 to 18 mm Hg). At the same time, mean arterial pressure (MAP) increased from 74 +/- 15 mm Hg (95% confidence intervals: 64 to 79 mm Hg) to 83 +/- 15 mm Hg (95% confidence intervals: 80 to 88 mm Hg) and left ventricular stroke work index from 22 +/- 10 g.m/m2 (95% confidence intervals: 19 to 25 g.m/m2) to 30 +/- 11 g.m/m2 (95% confidence intervals: 26 to 33 g.m/m2). There was no significant change in mean pulmonary artery pressure, pulmonary vascular resistance index, or systemic vascular resistance index. CONCLUSION: When cardiac pacing is required in critically ill patients, maintaining atrioventricular synchrony increases stroke volume, cardiac output, and MAP apparently with minimal effects on preload and afterload.

Acebutolol-induced ventricular tachycardia reversed with sodium bicarbonate.

BACKGROUND: Acebutolol is a unique beta blocker that possesses cardioselectivity, partial agonist activity, and membrane stabilizing activity. Sodium bicarbonate is used to reverse the cardiotoxic effects of other drugs with membrane stabilizing activity. There have been no reported cases of acebutolol-induced ventricular dysrhythmias treated successfully with bolus sodium bicarbonate. CASE PRESENTATION: A 48-year-old man ingested approximately 6.4 g of acebutolol with ethanol (blood ethanol 61 mmol/L). There were no other coingestants identified. One hour after presentation, the patient had a cardiac arrest with the monitor showing ventricular tachycardia. Sodium bicarbonate 50 mEq intravenous push converted the patient to sinus rhythm and the blood pressure improved to 129/90 mm Hg. CONCLUSION: This case demonstrates a temporal relationship between bolus sodium bicarbonate administration and the termination of acebutolol-induced ventricular tachycardia.

Frequency of lipid-lowering drug therapy after coronary and carotid operations for atherosclerosis.

BACKGROUND: Coronary artery bypass grafting (CABG) and carotid endarterectomy (CE) are palliative operations for patients with severe atherosclerosis of the coronary or carotid arteries. Secondary preventive measures after these operations have received little attention. METHODS: We conducted a retrospective observational study to determine the frequency of lipid-lowering drug therapy before and after CABG or CE done in 1997. RESULTS: Of the 204 patients who had CABG, 56 (27%) were receiving lipid-lowering drug therapy before admission, and 71 (37%) of 192 were discharged receiving it. Of the 59 patients who had CE, only 12 (20%) were taking a lipid-lowering drug before admission, and 8 (14%) upon discharge. Of those 59 patients, 23 (39%) had coronary artery disease. CONCLUSION: Secondary prevention after coronary or carotid operations for atherosclerosis has been underemphasized at our institution, prompting the establishment of a postoperative risk reduction program.

Comparison of transthoracic electrical impedance and thermodilution methods for measuring cardiac output.

Cardiac output was measured 120 times in 27 critically ill patients using the thermodilution and transthoracic electrical impedance methods. Both the minimum and mean values for the distance between the inner electrodes, and a variety of values for the resistivity of blood (rho) were substituted in the Kubicek's empiric formula for calculating cardiac output by transthoracic electrical impedance. Using the mean distance between the inner electrodes and a rho-value of 150 ohm X cm gave the best agreement between the methods (mean difference 0.17 +/- 2.4 L/min). Ventilation alone or with positive end-expiratory pressure did not significantly affect the bias of the estimate, but both affected its precision when compared with measurements in spontaneously breathing patients (SD of mean difference 2.4 and 3.2 L/min, respectively, vs. 1.5 L/min). The pulmonary artery wedge pressure was significantly higher in patients with an abnormal diastolic impedance waveform (zero-wave), but there was no relationship between wedge pressure and base impedance per unit length between the measuring electrodes.

Comparison of pulsed Doppler and thermodilution methods for measuring cardiac output in critically ill patients.

We obtained 145 consecutive cardiac output measurements in 38 critically ill patients, using the invasive thermodilution and the noninvasive pulsed Doppler methods. The mean thermodilution cardiac output (TDCO) was 5.7 +/- 1.87 L/min and the mean pulsed Doppler cardiac output (PDCO) was 5.16 +/- 1.66 L/min. The mean difference between the two measurements was 0.51 L/min with an SD greater than 1.6 L/min, reflecting the scattering of results. The overall correlation coefficient was .58. The intercepts were large and the regression equation some way from the line of equal values (TDCO = 2.28 + 0.66 PDCO). When the results were analyzed according to diagnosis or by group experience, there were some differences in the bias of the estimate; however, the SD of the difference between methods was greater than one liter/min in all groups. Thus, the pulsed Doppler method failed to estimate accurately TDCO in critically ill patients.

Usefulness of atrial electrograms recorded via central venous catheters in the diagnosis of complex cardiac arrhythmias.

OBJECTIVE: To assess the role of intravascular atrial electrograms in improving the diagnosis of complex cardiac arrhythmias in critically ill patients. DESIGN: Prospective, clinical study comparing the accuracy of cardiac rhythm diagnosis using standard surface electrocardiogram (EKG) and intravascular atrial electrograms. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: A total of 57 critically ill patients (44 cardiothoracic surgery, five acute myocardial infarction, two septic shock, six miscellaneous) with 85 complex cardiac arrhythmias that were unable to be diagnosed with certainty using the surface EKG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The intravascular atrial electrogram altered diagnosis based on the surface EKG in 11 (13%) patients and confirmed rhythm diagnosis in 60 (71%) of 85 patients with arrhythmia. Of 61 patients with wide complex tachycardia, 40 (66%) were diagnosed as ventricular tachycardia (atrioventricular dissociation demonstrated on the atrial electrogram), and 11 (18%) as supraventricular tachycardia with aberrant conduction. Ten (16%) wide complex tachycardias could not be diagnosed with confidence using both surface EKG and intravascular electrogram. There were no adverse effects with this technique. CONCLUSIONS: Intravascular atrial electrograms recorded via central venous catheters are useful in the diagnosis of complex cardiac arrhythmias, particularly ventricular tachycardia. The technique is safe, simple, and quick.