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We reviewed the post-mortem records of the Batticaloa Teaching Hospital and extracted data on all cases of fatal injury.
Amiodarone and sotalol facilitated successful electrocardioversion, which could be achieved in a stepwise fashion. Upon achievement of successful electrocardioversion, amiodarone is superior to placebo, and sotalol has a lesser effect. Antiarrhythmic drugs had no effect on the total number of energy step use in patients who had successful electrocardioversion. Calcium channel blockers had no influence on the success rate in achieving sinus rhythm. Successful electrocardioversion was associated with lower BMI and AF history < or =1 year. Lower energy use was associated with biphasic shocks, lower BMI, and AF duration < or =1 year.
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The results suggest that digoxin appears, through calcium-triggered signals, to reverse the reduced expression of PPARδ in H9c2 cells caused by HG treatment.
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The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose.
Improvements in equipment and diagnostic skills mean that more abnormalities can now be detected antenatally, thus increasing the demand for pregnancy termination at later stages of gestation. Potassium chloride injected into the fetal circulation is the most frequently used procedure. In this study, we propose a new method of feticide using injection of normal saline into the fetal pericardial space to induce cardiac tamponade, resulting in late fetal reduction with minimal maternal risk.
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A 15-year-old, Standardbred broodmare with an aortic sinus aneurysm developed rupture of the aneurysm with subsequent rupture of a tricuspid valve chorda tendinae, tricuspid regurgitation, acute right-sided congestive heart failure, and pulmonary thromboembolism. Shunting of blood from the aorta through the ruptured aneurysm into the right ventricle resulted in decreased renal perfusion and acute renal failure. Initially, treatment of the mare with analgesics, fluids, and digoxin resulted in clinical improvement, but the mare's condition deteriorated after 8 days and the mare was euthanatized due to unrelenting pain and a poor prognosis. Echocardiography was useful in diagnosis of the cardiac disease in the broodmare.
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We retrospectively analyzed the records of 80 patients who had atrial fibrillation during the postoperative period after cardiac surgery, initially divided in two groups: group A, 28 patients that used amiodarone, and group B composed of patients receiving digoxin. The latter group was divided further in a third group (C), with 21 patients in which amiodarone was associated with digoxin if there was no reversion of the arrhythmia after 48 hours of treatment. The observed differences were considered significant at P < 0.05.
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A significant serum level of digoxin-like immunoreactive substance (DLIS) (greater than or equal to 0.5 ng/ml) has been found in healthy full-term neonates, in prematurely born neonates as well as in full-term but small for gestational age neonates. Neither the babies nor their mothers had received digoxin therapy. On the first day of life, the incidence of serum levels of DLIS greater than or equal to 0.5 ng/ml in the three groups of neonates were respectively 64% (32/50), 42% (8/19) and 77% (10/13). Longitudinal measurements in preterm and small for gestational age neonates indicate a progressive disappearance of DLIS from their serum, none of them having a significant serum level at 21 days of age. As long as the chemical structure, origin and physiological properties of DLIS remain unknown, clinicians must be cautious in interpreting the serum levels of digoxin used for therapeutical purpose in neonates.
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The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.
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Commonly prescribed medications and over-the-counter supplements may influence prognosis among prostate cancer patients. Further well-designed pharmacoepidemiologic studies and randomized controlled trials of selected medications in appropriate patient groups are necessary before these drugs can bear new indications for prostate cancer treatment. We discuss considerations when deciding about use of these drugs in clinical practice at the present time.
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Digoxin-specific antibody fragments (DSFab) are used for the treatment of poisoning by cardiac glycosides, such as pharmaceutical digoxin. Dosing of this therapy for chronic and acute poisonings is based on the steady-state serum concentrations of digoxin, historical data in acute ingestions, or empiric regimens purportedly based on the average requirements. Empiric dosing for adult patients involves utilization of 3-6 vials for chronic poisoning and 10-20 vials for acute poisoning. The aim of this study was to describe the average dosing requirements based on the steady-state serum concentration of digoxin or historical data and compare this with the empiric dosing regimens. We performed a retrospective analysis of cases over an 11-year period presented to the Illinois Poison Center where administration of DSFab was recommended. We identified 140 cases of chronic digoxin poisoning and 26 cases or acute digoxin poisoning for analysis. The average dose of DSFab recommended in the cases of chronic digoxin poisoning was 3.05 vials (SD ± 1.31). The average dose of DSFab recommended in the cases of acute digoxin poisoning was 6.33 vials (SD ± 5.26). These values suggest that empiric dosing regimens may overestimate the need for DSFab in cases of both chronic and acute poisonings of pharmaceutical digoxin.
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In order to improve patient safety, systematic analysis of common and repetitive patterns of preventable adverse drug reactions (pADRs) in the clinical setting should be performed regularly in order to propose adequate prevention strategies. Our aim is to evaluate the preventability of all ADRs collected in a drug information research center database, by spontaneous reporting and clinical surveillance in two internal medicine departments. One reviewer systematically reevaluated all the cases stored in the database. ADRs were deemed preventable if they were due to: a contraindication, an inadequate dose, a drug interaction, an inappropriate prescribing decision for the patient's condition, inadequate monitoring, self-medication, or non-adherence to therapy. Out of 251 ADRs evaluated, 103 (41 %) were considered preventable. Out of the total pADRs, 86.4 % were serious. The most frequent adverse outcomes affected the gastrointestinal system (21.4 %), followed by the renal (11.6 %), metabolic (10.7 %), vascular (10.7 %) and hepatic (6.8 %) systems. Acenocoumarol (28 %), diclofenac (12.6 %), digoxin and furosemide accounted for more than 50 % of all preventable reports. One of up to three factors was involved in the preventability of the analyzed reports. Drug-drug interactions were the cause of 49.5 % of the pADRs. Inappropriate dose accounted for 17.5 % reports out of the total pADRs, inappropriate monitoring for 9.7 % reports, history of allergy to drug or drug class for 5.8 % reports and administration of a contraindicated drug for 4.8 % reports. Identifying prevalent pADRs in this study indicates a clear target for prevention strategies: drug prescription, with a special emphasis on drug interactions.
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Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.
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When taken together, these studies show that NHE-1 inhibition attenuates the hypertrophic effect of cardiac glycosides without affecting inotropic parameters and suggest a possible approach to limiting glycoside-induced hypertrophic responses while preserving therapeutic, i.e. inotropic, actions.
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1. A ouabain-displacing factor (ODF) was measured in the urine of non-pregnant, normotensive pregnant and hypertensive pregnant women by a receptor-binding assay with sodium, potassium-dependent adenosine triphosphatase. 2. Urinary ODF was significantly increased in normal pregnancy. 3. Greater increases were seen in pregnancy-induced hypertension and pre-eclampsia.
Twenty-one children with EFE were randomly divided into two groups: (1) treated with traditional regimen (digoxin, prednisone and/or diuretics) (n = 10); (2) treated with carvedilol plus traditional regimen (n = 11). Measurement of plasma concentration of BNP by ELISA, cardiac function by ultrasound were performed before and after 6 months of treatment. The changes in clinical symptom, heart rate, heart function, side effect and maximal tolerance dose after treatment with carvedilol were observed.
Flecainide acetate has a recognized proarrhythmic effect in patients treated for ventricular tachycardia. Three patients developed severe ventricular arrhythmias while taking flecainide for atrial fibrillation. Patient 1 had normal ventricular function and idiopathic atrial fibrillation. Treadmill exercise tests during digoxin therapy showed no ventricular arrhythmia; however, during flecainide therapy the patient developed ventricular flutter at his peak exercise level that required cardioversion. Patient 2 had normal ventricular function and a prosthetic mitral valve. During therapy with flecainide, 150 mg twice daily, he had an episode of sustained ventricular tachycardia, also at his peak exercise level. Patient 3 had paroxysmal atrial fibrillation and hypertrophic cardiomyopathy but no previous ventricular arrhythmia. She died suddenly within 10 days of starting flecainide therapy. Judged from previous findings none of these patients was considered at high risk for proarrhythmia. These cases suggest a possible relation between vigorous exercise, atrial fibrillation, and the proarrhythmic properties of flecainide and indicate the limitations of classifying patients as "high-risk" or "low-risk" for proarrhythmic complications of anti-arrhythmic therapy.
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Even after implementation of current clinical guidelines, addition of spironolactone therapy provides an opportunity to further reduce the large clinical and economic burden of patients with heart failure.
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Polarized cellular systems coexpressing Ad3A4, AdRed, and the MDR1/Pgp transporter were developed and characterized. The results document the utility of these polarized model systems for simultaneous drug transport/drug metabolism studies. Since the experimental approach can be adapted to study the interplay of multiple enzyme/ transporting systems, it may find significant application as a screening tool for the pharmaceutical industry and as a more basic research tool to study the kinetics of intestinal drug bioavailability.
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A case of serial killing by poisoning by a 59-year-old practical nurse is discussed. Following a report by an emergency-room doctor of an attempted murder, police performed an investigation into all deaths of patients in the nurse's care. Earlier, a medico-legal cause-of-death investigation had been performed on two of these cadavers, but in the other three cases the death certificate had been issued after a medical investigation only. In two of these latter cases, the body had been cremated, but fixed histological samples taken at medical autopsy were available, while in one case the person had died recently and the body was thereafter exhumed and autopsied. All of the suspected victims were older people who required nursing, and the nurse's course of action was consistent in all cases. In the absence of ordinary post-mortem toxicology samples in the medical cases, extraordinary evidence--paraffin-embedded liver tissue samples originally taken for histology at autopsy--was successfully recovered in two cases and analyzed for drugs. In all five cases, drugs not prescribed to the patient were detected, including digoxin, dixyrazine, citalopram, venlafaxine, and benzodiazepines (diazepam, chlordiazepoxide, temazepam, and oxazepam). The nurse was eventually found guilty of five murders by poisoning, five attempted murders, and three aggravated assaults. The nurse was sentenced to life imprisonment.
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No studies have been conducted on rational drug use among children in Uzbekistan. This study aimed to analyze drug uses based on pharmaco-epidemiologic (PE) data from Regional Children's Multi-Profile Medical Centre (RCMPMC) in Andijan, Uzbekistan. Our study assessed drug usage in children with cardiovascular (CV) diseases, without intervening in the treatment processes or in the course of the diseases.
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(1) The treatment aims in atrial fibrillation are to reduce patients' symptoms and to prevent both embolism and deterioration of any underlying heart disease. Therapy consists of anticoagulant or antiplatelet drugs, treatment of any underlying heart disease, and heart rate control. (2) Digoxin, betablockers, diltiazem and verapamil slow the heart rate but rarely restore sinus rhythm. Amiodarone, disopyramide, flecainide, quinidine and sotalol can be used to prevent relapse of atrial fibrillation after electrical cardioversion, but they all have potentially serious adverse effects. New trials of antiarrhythmic treatments have been published since our last review of this subject. (3) In one trial in 403 patients, amiodarone was more effective than sotalol and propafenone in restoring and maintaining sinus rhythm. After 15 months of follow-up, there were fewer strokes among patients treated with amiodarone, but there was no difference between the three drugs in the overall incidence of cardiovascular events. (4) A clinical trial with 4060 patients compared rhythm control (mainly with amiodarone, sotalol or propafenone; sometimes combined with electrical cardioversion) and rate control (with digoxin, betablocker, diltiazem or verapamil; systematically combined with anticoagulant therapy). The antiarrhythmic treatment restored sinus rhythm in more than half the patients in the long term. But rhythm control did not reduce the risk of death or serious cardiovascular events during a mean follow-up period of 3.5 years. Rhythm control caused more adverse events than rate control; subgroup analyses (weak evidence) suggest that rhythm control may also have caused more deaths among patients over 65 and among patients with coronary heart disease. (5) In another trial, electrical cardioversion followed by antiarrhythmic therapy (mainly sotalol) sustainably restored sinus rhythm in more than one-third of 522 patients. But, compared with rate control treatment plus anticoagulant therapy, rhythm control did not reduce the risk of cardiovascular events, and was associated with a larger number of serious adverse cardiac effects. (6) Other recent trials confirm the risk of serious adverse effects, including severe arrhythmia with sotalol (especially at the start of treatment), and adverse thyroid and pulmonary effects with amiodarone. (7) Combined radiofrequency ablation and cardiac stimulation improved symptoms in some patients with incapacitating atrial fibrillation who had not responded to other treatments. However, this approach carries a risk of serious adverse effects, and its impact on the risk of cardiovascular events and death is not known. (8) In practice, an attempt should be made to restore sinus rhythm with amiodarone and/or electrical cardioversion, in symptomatic, recent or paroxysmal atrial fibrillation in patients under 65 who have no signs or symptoms of coronary heart disease. In other situations, rate control is the first-line option, using digoxin, betablockers (other than sotalol) or calcium channel blockers (diltiazem or verapamil). Whatever the option, treatment must be combined with anticoagulant or antiplatelet therapy, and with treatment of any underlying heart disease.
Only double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure were eligible for inclusion.
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This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).
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Analyses of the pharmacokinetics of digoxin were conducted using the nonlinear mixed-effects modelling (NONMEM®) software, a computer program designed to analyse pharmacokinetics in study populations by allowing pooling of data. Steady-state data (140 observations) obtained by routine therapeutic drug monitoring following repeated oral administration of digoxin in 94 hospitalized elderly patients (age ≥65 years) were analysed to establish the role of patient characteristics in estimating doses of digoxin for elderly patients.
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This study was performed to test the effect of dialysis-induced acute modifications of plasma volume and sodium pool on red blood cell (RBC) ion transport in patients with end-stage renal disease. This approach confirmed the presence of an Na-K pump inhibitor in the plasma of uremic patients with extracellular fluid volume expansion. This factor cross-reacts with digoxin antibodies, and its concentration decreases during dialysis; this explains the increased activity of the RBC Na-K pump that is consistently observed during dialysis.
Placenta tissues from obese and lean women were collected. Female C57BL mice were fed with either a normal chow diet or a high-fat diet for 12 weeks before mating and throughout pregnancy. Maternal plasma glucose, HDL-C, LDL-C, TC, TGs, insulin, IL-1β, IL-6 and TNF-α concentrations was detected. Placental ABCB1/Abcb1a/Abcb1b/IL-1β/IL-6/TNF-α mRNA and P-gp/IL-1β/IL-6/TNF-α protein expression were determined by real-time quantitative PCR and western-blot, respectively. Maternal plasma and fetal-unit digoxin concentrations were detected by a commercial kit assay.
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In managing atrial fibrillation, the main therapeutic strategies include rate control, termination of the arrhythmia, and pr vention of recurrences and thromboembolic events. Rate control with digoxin, b-blockers, verapamil, and diltiazem may be preferred in drug refractory and sedentary patients with markedly dilated left atrium and atrial fibrillation of long duration. Drugs useful in the maintenance of sinus rhythm include quinidine, procainamide, disopyramide, sotalol, amiodarone, dofetilide, flecainide, and propafenone. In patients with structural heart disease, the class III antiarrhythmics are the initial drugs of choice, given their neutral effects on survival in a post-myocardial infarction and congestive heart failure population. Due to high recurrence rates with pharmacologic therapy, nonpharmacologic options of therapy include atrioventricular junction ablation, atrial defibrillators, catheter ablation of pulmonary vein foci, and attempts to perform an atrial Maze procedure using catheters. Hybrid therapy using drugs in combination with nonpharmacologic approaches will be used more frequently in the future for refractory patients.
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Initially, the patients had a 23.9% increase in the levels of factors VII and X, a 14.3% decrease of antithrombin III, 29.8 and 227.6% rise in concentrations of fibrinogen and SFMC, respectively, compared to controls. Aftertreatment values of fibrinogen, factors VII and X, SFMC fell by 21.1, 17 and 35.5%, respectively. The thrombin time arose by 17.9% (p > 0.05). Insignificant inhibition was registered in the activity of acid phosphotase and gamma-GT. Glucose, AST, ALT, LDH levels remained unchanged. Plasma creatinine tended to lowering. Total cholesterol insignificantly increased at high levels of HDL cholesterol (p > 0.05) and reduced levels of triglycerides (p > 0.05).
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Since the pharmacokinetics and pharmacodynamics of a single dose of warfarin and the steady-state pharmacokinetics of digoxin were not affected by coadministration of solifenacin in healthy subjects, the need for dosing adjustments for digoxin and/or warfarin does not seem warranted.