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Biomedical subjects

C M White

Publications and source records attributed to C M White.

At least 19 recordsLinked to original sources
PubMed2001

Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.

BACKGROUND: Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery. METHODS: We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5. FINDINGS: Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar. INTERPRETATION: Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.

Administration, Oral↗
PubMed2001

A placebo controlled evaluation of the antifibrillatory effects of carvedilol.

This article evaluates the antifibrillatory effects of carvedilol 5 mg/kg and vehicle (dimethyl-formamide) over time. Sprague-Dawley rats were anesthetized and intubated. They underwent baseline ventricular fibrillation threshold (VFT) determination and then received 1 of the 2 treatments (n = 10/group) over 8 minutes. VFT and determinations were performed at 2, 7, 15, 30, 45, and 60 minutes postinfusion. Carvedilol significantly increased the VFT at 2, 7, 15, 30 minutes versus baseline and the vehicle control group. Carvedilol significantly reduced the heart rate and the mean arterial pressure at every evaluable time point versus baseline and vehicle control. Carvedilol showed significant antifibrillatory effects versus baseline and vehicle for the first 30 minutes but not thereafter, even though the heart rate and mean arterial pressure remain significantly reduced.

Adrenergic beta-Antagonists↗
PubMed2001

Evaluation of CYP2D6 oxidation of dextromethorphan and propafenone in a Chinese population with atrial fibrillation.

The objective of this study was to determine the percentage of patients with paroxysmal atrial fibrillation who were poor metabolizers of CYP2D6 in a Chinese population from Hong Kong and to assess the relationship between the dextromethorphan/dextrorphan ratio and the propafenone/5-hydroxypropafenone ratio or the steady-state propafenone concentration. Patients (n = 60) were recruited from the Arrhythmia Clinic at the University of Hong Kong and given dextromethorphan 30 mg. The dextromethorphan and dextrorphan concentrations in urine over the next 8 hours were used to determine metabolizer status. If the metabolic ratio was greater than 0.3, the patient was determined to be a poor metabolizer. In phase 2, patients (n = 38) were given propafenone 150 mg twice daily, and at steady state, the propafenone and 5-OH propafenone plasma concentrations were determined. It was found that 15% of the patients were poor metabolizers of dextromethorphan. There was a significant correlation between the metabolic ratios of dextromethorphan/dextrorphan and propafenone/5-OH propafenone (r = 0.49, p = 0.0019) and between the dextromethorphan/dextrorphan ratio and the concentration of propafenone (r = 0.32, p = 0.05). No correlations were found in the extensive or poor metabolizer subgroups. It was concluded that the percentage of poor metabolizers in atrial fibrillation patients from Hong Kong was much larger than in previous studies of Chinese patients who were not from Hong Kong. The ability to metabolize dextromethorphan to dextrorphan is related to the ability to metabolize propafenone to 5-hydroxypropafenone.

Anti-Arrhythmia Agents↗
PubMed2001

Do HMG-CoA reductase inhibitors affect fibrinogen?

OBJECTIVE: To review commonly used fibrinogen assay methods and the evidence demonstrating an association between fibrinogen and increased risk of coronary artery disease and to review the current literature to determine and assess the impact of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on fibrinogen. DATA SOURCES: Primary and review articles identified from a MEDLINE search (1966-December 1999); references obtained from these publications were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All articles were evaluated, and all relevant information was included in this review. DATA SYNTHESIS: The Clauss method is currently the preferred method for determining plasma fibrinogen concentrations, due to its high degree of accuracy and precision. Furthermore, unlike immunologic methods, its reliability is unaffected by change in triglycerides. The effects of four HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin, pravastatin) on fibrinogen have been evaluated. Atorvastatin has been shown to induce significant increases in fibrinogen (22% increase; p <0.05) by using the immunonephelometric method. This method also demonstrated that lovastatin use was associated with a 24.4% increase (p < 0.0001) in plasma fibrinogen concentration. Simvastatin has been shown in multiple studies using the Clauss method to have a neutral effect on fibrinogen. The majority of studies have revealed significant decreases (7-19%) in fibrinogen following treatment with pravastatin. CONCLUSIONS: Future studies need to be performed evaluating the effects of HMG-CoA reductase inhibitors on fibrinogen, but using direct comparisons and clotting assay methodology.

Animals↗
PubMed2000

Evaluation of the effectiveness of DNA-binding drugs to inhibit transcription using the c-fos serum response element as a target.

Previous work has demonstrated that sequence-selective DNA-binding drugs can inhibit transcription factors from binding to their target sites on gene promoters. In this study, the potency and effectiveness of DNA-binding drugs to inhibit transcription were assessed using the c-fos promoter's serum response element (SRE) as a target. The drugs chosen for analysis included the minor groove binding agents chromomycin A(3) and Hoechst 33342, which bind to G/C-rich and A/T-rich regions, respectively, and the intercalating agent nogalamycin, which binds G/C-rich sequences in the major groove. The transcription factors targeted, Elk-1 and serum response factor (SRF), form a ternary complex (TC) on the SRE that is necessary and sufficient for induction of c-fos by serum. The drugs' abilities to prevent TC formation on the SRE in vitro were nogalamycin > Hoechst 33342 > chromomycin. Their potencies in inhibiting cell-free transcription and endogenous c-fos expression in NIH3T3 cells, however, were chromomycin > nogalamycin > Hoechst 33342. The latter order of potency was also obtained for the drugs' cytotoxicity and inhibition of general transcription as measured by [(3)H]uridine incorporation. These systematic analyses provide insight into how drug and transcription factor binding characteristics are related to drugs' effectiveness in inhibiting gene expression.

3T3 Cells↗
PubMed2000

Angiotensin-converting-enzyme inhibition in heart failure or after myocardial infarction.

The use of angiotensin-converting-enzyme (ACE) inhibitors in patients with heart failure and after myocardial infarction (MI) is discussed, and results of relevant studies are reviewed. In several large trials, the administration of captopril or lisinopril within the first 36 hours after the onset of chest pain due to MI was associated with significant reductions in mortality risk, compared with placebo. Trials evaluating the use of captopril, ramipril, or trandolapril at least three days after the onset of chest pain due to MI also demonstrated significant reductions in mortality risk. Pivotal clinical trials of captopril, enalapril, lisinopril, and ramipril in the treatment of heart failure are presented. Overall, ACE inhibitor therapy was shown to reduce mortality by decreasing the progression of heart failure. Possible benefits of ACE inhibition in addition to reductions in afterload and preload and preservation of serum potassium are discussed. Certain ACE inhibitors may exert positive effects by modulating plasminogen activator inhibitor-1, endothelial function, and left ventricular remodeling. If not contraindicated, long-term therapy with captopril, lisinopril, or ramipril should be used in post-MI patients. Patients with heart failure should be treated with one of the ACE inhibitors that have been shown beneficial for this indication.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Repeated stimuli for axonal growth causes motoneuron death in adult rats: the effect of botulinum toxin followed by partial denervation.

Axons of motoneurons to tibialis anterior and extensor digitorum longus muscles of adult rats were induced to sprout by injecting botulinum toxin into them, by partial denervation or by a combination of the two procedures. Ten weeks later, the number of motoneurons innervating the control and operated tibialis anterior and extensor digitorum longus muscles was established by retrograde labelling with horseradish peroxidase. In the same preparations, the motoneurons were also stained with a Nissl stain (gallocyanin) to reveal motoneurons in the sciatic pool. Examination of the spinal cords from animals treated with botulinum toxin showed that the number of retrogradely labelled cells and those stained with gallocyanin in the ventral horn on the treated compared to the control side was unchanged. In rats that had their L4 spinal nerve sectioned on one side, the number of retrogradely labelled cells on the operated side was 48+/-3% (n = 5) of that present in the control unoperated ventral horn. Thus, just over half the innervation was removed by cutting the L4 spinal nerve. Counts made from gallocyanin-stained sections showed that 94+/-4% (n = 5) of motoneurons were present in the ventral horn on the operated side. Thus, section of the L4 spinal nerve did not lead to any death of motoneurons. In rats that had their muscles injected with botulinum toxin three weeks prior to partial denervation, the number of retrogradely labelled cells was reduced from 48+/-3% (n = 5) to 35+/-4% (n = 5). Moreover, only 67+/-5% (n = 5) of motoneurons stained with gallocyanin, suggesting that a proportion of motoneurons died after this combined procedure. This result was supported by experiments in which motor unit numbers in extensor digitorum longus muscles were determined by measurements of stepwise increments of force in response to stimulation of the motor nerve with increasing stimulus intensity. In partially denervated extensor digitorum longus muscles, 16.6+/-0.7 (n = 5) motor units could be identified, and in animals treated with botulinum toxin prior to partial denervation only 13.3+/-0.9 (n = 3) motor units were present. Taken together, these results show that treatment with botulinum toxin followed by partial denervation causes motoneuron death in adult rats.

Animals↗
PubMed2000

The effect of testosterone on health-related quality of life in elderly males - a pilot study.

OBJECTIVE: To assess the effect of short-term testosterone supplementation on health-related quality of life in elderly males. METHOD: As part of a double-blind, placebo-controlled study, healthy males > or = 65-year-old were randomised to receive a total of four doses of 200 mg testosterone enanthanate (n = 14) or placebo (n = 8) intramuscularly every 2 weeks. Health-related quality of life (HRQOL) was assessed using the Short Form 36-item (SF-36) and Psychological General Well-Being (PGWB) scales, at baseline, week 8 and during therapy withdrawal, 6 weeks after the last dose. RESULTS: The baseline SF-36 scores were similar between the groups in seven domains; only vitality was significantly lower in the placebo group (T: 80.4, P: 65.6; P = 0.007). After the 8-week treatment period and withdrawal phase, SF-36 scores were not significantly different between the groups. The PGWB scores at baseline, on treatment and off treatment were not significantly different between the groups. Moreover, the SF-36 and PGWB scores within each group did not change significantly over time. CONCLUSION: This pilot study suggests that intramuscular testosterone, administered at a dose of 200 mg every 2 weeks, does not affect the HRQOL of elderly males.

Aged↗
PubMed2000

Efficacy and cost analysis of ibutilide.

OBJECTIVE: To determine the efficacy and safety of ibutilide in atrial fibrillation (AF) and atrial flutter (AFl) in a clinical setting and to compare the cost of first-line ibutilide with that of projected first-line electrical cardioversion (EC) from a hospital and third-party payer perspective. METHODS: Medical records of all patients (n = 60) who received ibutilide from August 1996 to March 1998 were reviewed. Efficacy was defined as successful conversion to sinus rhythm within 60 minutes of the end of the infusion, and the maintenance of sinus rhythm until hospital discharge. Safety was evaluated by determining the incidence of torsade de pointes. Charges for EC and drug administration were obtained from the hospital database and converted to costs using cost/charge ratios. Hospital costs included drug, drug administration, cardiac intensive care laboratory fee, and the cost of managing torsade de pointes. The third-party payer calculation included all of the above plus the cardiologist and anesthesiologist fees. RESULTS: Fifty percent of patients with AF or AFl were successfully converted with ibutilide; 67% of these remained in sinus rhythm at hospital discharge. Three patients experienced nonsustained torsade de pointes; all resolved with pharmacologic management. From a hospital perspective, the cost of first-line ibutilide was greater than the cost of first-line EC ($280 vs. $138 per patient). However, from a third-party payer perspective, the use of ibutilide saved approximately $324 per patient ($718 vs. $1042). CONCLUSIONS: The efficacy and safety of ibutilide in the clinical setting are consistent with data reported in clinical trials. In contrast to a previous decision analysis, ibutilide was not associated with cost savings from a hospital perspective, but was from a payer perspective.

Aged↗
PubMed2000

Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine-induced myocardial ischemia.

STUDY OBJECTIVE: To determine the effect of metoprolol on dobutamine stress testing with technetium-99m sestamibi single-photon emission computed tomography imaging and ST-segment monitoring, and to assess the impact of intravenous glucagon on metoprolol's effects. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community hospital. PATIENTS: Twenty-two patients with known reversible perfusion defects. INTERVENTION: Patients underwent dobutamine stress tests per standard protocol. Before dobutamine was begun, no therapy was given during the first visit, and patients were randomized on subsequent visits to receive metoprolol or metoprolol plus glucagon 1 mg. Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats/minute or a total intravenous dose of 20 mg. MEASUREMENTS AND MAIN RESULTS: Metoprolol reduced maximum heart rate 31%, summed stress scores 29%, and summed difference scores 43% versus control. Metoprolol plus glucagon also reduced the maximum heart rate 29% versus control. Summed stress and summed difference scores were not significantly reduced, although they were 18% and 30% lower, respectively, than control. No significant differences were found in any parameter between metoprolol and metoprolol-glucagon. CONCLUSION: During dobutamine stress testing, metoprolol attenuates or eliminates evidence of myocardial ischemia. Glucagon 1 mg, although somewhat effective, does not correct this effect to the extent that it can be administered clinically.

Adrenergic beta-Agonists↗
PubMed2000

Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists.

Over the past 4 years, six angiotensin II receptor antagonists (ARBs) were approved for treating essential hypertension. They differ with respect to dosing, metabolism, elimination, clinical efficacy, and investigational applications. Candesartan cilexetil is the only prodrug among the agents. Losartan is distinguished from other ARBs by cytochrome P450 (CYP) 3A4- and CYP2C9-mediated biotransformation to its active metabolite EXP-3174. No ARB requires dosage adjustment for renal impairment, but the initial dose of losartan should be reduced 50% in hepatically impaired patients. None of the drugs is significantly cleared by hemodialysis. Completion of continuing trials will elucidate the drugs' role in treating heart failure, cerebral stroke, and myocardial infarction.

Angiotensin Receptor Antagonists↗
PubMed2000

A review of pathophysiology and therapy of patients with vasovagal syncope.

Vasovagal syncope is a common disorder that can compromise quality of life and lead to significant morbidity. It is characterized by an initial exaggerated sympathetic output followed by parasympathetic activation and sympathetic withdrawal, as shown by diagnostic head-up tilt (HUT) table testing. Numerous drugs have been evaluated for treating this disorder. beta-Blockers are well studied and commonly administered but are specifically more efficacious in patients with isoproterenol HUT than in those with regular HUT. The role of the serotonergic system has captured new interest. Selective serotonin reuptake inhibitors show promising results in preventing vasovagal syncope in treatment-refractory patients. Also, new investigations suggest that serotonin receptor antagonism may be beneficial. Despite these findings, definitive treatment does not exist.

Humans↗
PubMed2000

Assessment of the drug interaction between alteplase and nitroglycerin: an in vitro study.

Alteplase is the most commonly administered thrombolytic agent in the United States. However, concurrent therapy with nitroglycerin reduces plasma alteplase concentrations and its clinical efficacy. We sought to determine if this interaction is concentration and pH dependent. Seventy plasma samples were prepared and divided into three groups: alteplase 500 IU/ml alone (group 1), alteplase 500 IU/ml plus nitroglycerin 5 ng/ml (group 2), and alteplase 500 IU/ml plus nitroglycerin 200 ng/ml (group 3). The samples were analyzed at time zero and 3 hours (incubated at 37 degrees C). Group 1 had significantly higher plasma alteplase concentrations than group 3 (p<0.001). When alteplase and nitroglycerin are combined, the degradation of alteplase in plasma is enhanced.

Data Interpretation, Statistical↗
PubMed2000

An evaluation of the hemostatic effect of externally applied notoginseng and notoginseng total saponins.

No effective hemostatic agents are available for external use. This project was conducted to evaluate the hemostatic effects of notoginseng using a hemorrhagic rat model. Rats (n = 40) were divided into four groups, and their tails were transected 5 mm from the tip. Group 1 received no treatment (control), while the other groups received external powder applied to the wound. Group 2 received placebo (flour), group 3 received ground notoginseng, and group 4 received a saponin extract of notoginseng. The total bleeding time was determined and compared between groups. The notoginseng group had lower bleeding times (9.60 +/- 1.50 min) than the control group (19.23 +/- 4.09 min, p < 0.001) or the placebo group (15.18 +/- 2.24 min, p < 0.001). Likewise, the saponin extract group had significantly lower bleeding times (11.70 +/- 2.53 min) than the control and placebo groups (p < 0.001 for both comparisons). No differences were found between the notoginseng and the saponin extract groups (p = 0.35). Notoginseng and a saponin extract from notoginseng provide hemostatic effects when applied externally.

Analysis of Variance↗