Six infants (3 M, 3 F, mean age 42 +/- 62 days, range 1-150) affected with atrial flutter without structural heart disease were studied and then acutely and chronically treated. The effectiveness of chronic antiarrhythmic treatment was evaluated with Holter monitoring every 3 months for the first year of life and with transesophageal atrial pacing.
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Fetal echocardiography has progressed to be able to diagnose many forms of congenital heart disease (CHD) and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. Fetal echocardiography is for pregnancies at risk of structural, functional, and rhythm-related fetal heart disease. Routine obstetrical ultrasound screening is critical in the prenatal detection of fetal heart disease/CHD. With or without CHD, fetal heart dysfunction defined as inadequate tissue perfusion may occur. Perinatal problems other than CHD can also be assessed, such as the effects of noncardiac malformations that affect hemodynamics, that is, twin-twin transfusion. Cardiac rhythm can affect cardiac function and outcome, and prenatal diagnosis can be lifesaving. A tool for the assessment of cardiac function is the Cardiovascular Profile Score that combines ultrasonic markers of fetal cardiovascular unwellness based on univariate parameters, which have been correlated with perinatal mortality. This "heart failure score" could potentially be used in much the same way as and in combination with the biophysical profile score. This study will present a summary of fetal Doppler and its place in the diagnosis and assessment of prognosis of fetal heart failure.
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Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.
A systematic literature review was conducted using MEDLINE, CINAHL, PubMed, PsycINFO, and Cochrane Library to identify publications from August 1973 to June 2013. Keywords were accidental falls, heart failure, fall rates, fall injuries, and fall risk. Inclusion criteria were publications that were primary data based, included heart failure sample, had falls/fall risk as study variables, and were written in English language. Exclusion criteria were quality improvement/evaluation, case reports/studies, news, opinions, narrative reviews, meeting reports, reflections, and letters to editors. Data were abstracted using a standardized data collection form.
In a population-based nation-wide pharmaco-epidemiological case-control design, we compared 124,655 patients that sustained a fracture during 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders.
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A cross-section study with systematic selection of the study sample. All 32,051 outpatients seen on the same day by 1,159 physicians specialized in primary-care (79%) and cardiology (21%) were prospectively added to a database including history of cardiac disease (heart failure, coronary disease or atrial fibrillation), blood pressure, and ongoing treatment.
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To track the pharmacokinetic features of red ginseng (RG), a rapid and sensitive ultra fast liquid chromatographic coupled with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous quantification of twenty-one ginsenosides and their three aglycones, including 18 prototype compounds (ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, Rg5, Rh4, Rk1, Rk3, 20(S)-Rf, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(R)-Rh1, 20(S)-NG-R2), and 6 metabolites (ginsenosides 20(S)-Rh2 and Rh3, 20(S)-protopanaxadiol (PPD), 20(S)-protopanaxatriol (PPT), 20(R)-PPT, ginseng saponin compound K) of RG in rat plasma after oral administration of RG water extract at a single dose of 4g/kg body weight to rats. All analytes with internal standard (digoxin) were detected by multiple reaction monitoring in negative ionization mode and separated on an ACQUITY UPLC(®) BEH RP-C18 column (1.7μm, 100×2.1mm). This established method was well validated in terms of linearity, sensitivity, intra- and inter-day precisions, accuracy, recovery, matrix effect, stability, and had a lower limit of quantification at the concentration range of 0.12-8.12ng/mL for all of analytes. This UFLC-MS/MS approach was successfully applied to the pharmacokinetic study for RG water extract in rats. We firstly proposed that Rb1, Rb2, Rc, Rd, Rg1, Rg5, 20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD measured in rat plasma were suitable pharmacokinetic markers of RG extract in rats due to their high systemic exposure levels. Thus, this specific and reliable method will be useful for future applications to pharmacokinetic studies for various sources of ginsenoside samples and Panax herbs in vivo.
The present study characterized CYP3A4-Caco-2 cell monolayers when induced for 24 h in the presence of both NaB and TPA. These conditions provide intact cells with significant CYP3A4 and P-gp expression suitable for the concurrent study of transport and metabolism.
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Heart failure (HF) with preserved ejection fraction (EF) has a high prevalence in the geriatric population, and this cohort may be at risk of complications caused by polypharmacy. Effects of commonly used cardiac medications on long-term survival of patients >80 years with HF and preserved left ventricular EF were assessed. One hundred forty-two patients were evaluated. During a 5-year follow-up, 98 patients died (69%). There were no significant differences in baseline parameters in patients who died compared with those who survived at 5 years. None of the drug therapies appeared to make a significant difference in long-term survival, including beta blockers (p = 0.89), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (p = 0.91), calcium channel blockers (p = 0.69), diuretics (p = 0.30), digoxin (p = 0.22), and statins (p = 0.32). In conclusion, based on the present data, it appears that use of certain common cardiac medications may not be associated with a significant effect on long-term survival in octogenarians with HF and preserved EF.
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We evaluated the effect of acetaminophen (APAP), given as a single, 1g/kg body weight dose, on expression and activity of rat liver multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp), two major canalicular drug transporters. The studies were performed 24h after administration of the drug. APAP induced an increase in plasma membrane content of Mrp2 detected by western blotting, consistent with increased detection of the protein at the canalicular level by immunoflourescence microscopy. In vivo biliary excretion of dinitrophenyl-S-glutathione, a well known Mrp2 substrate, was slightly but significantly increased by APAP, agreeing well with upregulation of the transporter. Basal biliary excretion of oxidized glutathione, an endogenous Mrp2 substrate, was also increased by APAP, likely indicating increased hepatic synthesis as a result of APAP-induced oxidative stress followed by accelerated canalicular secretion mediated by Mrp2. APAP also increased the expression of P-gp detected by western blotting and immunofluorescence microscopy as well as the in vivo biliary secretory rate of digoxin, a model P-gp substrate. Because specific APAP-conjugated metabolites are Mrp2 substrates, we postulate that induction of Mrp2 by APAP may represent an adaptive mechanism to accelerate liver disposition of the drug. In addition, increased Mrp2-mediated elimination of oxidized glutathione may be essential in maintaining the redox equilibrium in the hepatocyte under conditions of APAP-induced oxidative stress.
Herbal medicines are mixtures of more than one active ingredient. The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb-drug interactions is theoretically higher than drug-drug interactions, if only because synthetic drugs usually contain single chemical entities. Case reports and clinical studies have highlighted the existence of a number of clinically important interactions, although cause-and-effect relationships have not always been established. Herbs and drugs may interact either pharmacokinetically or pharmacodynamically. Through induction of cytochrome P450 enzymes and/or P-glycoprotein, some herbal products (e.g. St John's wort) have been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of conventional drugs, including cyclosporine, indinavir, irinotecan, nevirapine, oral contraceptives and digoxin. The majority of such interactions involves medicines that require regular monitoring of blood levels. To date there is less evidence relating to the pharmacodynamic interaction. However, for many of the interactions discussed here, the understanding of the mechanisms involved is incomplete. Taking herbal agents may represent a potential risk to patients under conventional pharmacotherapy.
Taken together, these findings suggest that cryptotanshinone and dihydrotanshinone could be further developed for sensitizing resistant cancer cells and used as an adjuvant therapy together with anticancer drugs to improve their therapeutic efficacies for colon cancer.
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Before and after observational study, with two periods of 28 days each (P1 in 2008, P2 in 2009), with educational seminars on Beers criteria provided between them. All patients >65 years that were admitted during both time periods in health centres with a single dose drug system were included, taking data on those with inadequate prescriptions.
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The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.
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It is widely but not unanimously accepted that one or more endogenous digitalis-like factors (EDLF) circulate in human plasma. In this paper we provide confirmatory evidence that newborn plasma contains a factor with immunological and biological properties similar to ouabain and demonstrate that this factor may be present also in the adult. In fact, we obtained in newborn and adult plasma extracts, identical HPLC elution profiles of ouabain-like immunoreactivity and 86Rb erythrocyte uptake inhibitory activity with a major peak corresponding to the retention time of ouabain. The fact that immunoreactivity and biological digitalis-like activity in the peak are due to an identical substance is strongly supported by the correlation between RIA and 86Rb uptake inhibitory values observed in the purified fractions. Finally, the strong correlation between immunoreactivity observed in plasma samples after simple SepPak C18 extraction and after additional HPLC suggests that less purified samples may be assayed for screening purposes. However, for a more quantitative assessment, this simple extraction method needs a subsequent HPLC purification for eliminating an overestimation of values due to cross-reacting impurities.
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We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables.
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Inadequately controlled AF is associated with a higher rate of mortality. Optimization of therapeutic strategies for the rate control of AF remains determined.
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Cohort study with 1 to 17 months of followup.
Atrial reentry tachycardia is common after surgical repair of congenital heart disease. The arrhythmia is often difficult to treat and is occasionally life-threatening. This study reports experience with atrial antitachycardia (AAIT mode) pacing for the management of atrial reentry tachycardia, with emphasis on the risks and benefits of automatic pacing therapy. Eighteen patients (2-32 years of age) with a variety of congenital heart lesions underwent atrial antitachycardia pacemaker placement for recurrent atrial tachycardia that was amenable to pace termination prior to the implantation procedure. An appropriate antitachycardia program was determined by repeated induction and termination of atrial tachycardia using the noninvasive programmed stimulation mode of the pacemaker. Over 4-30 months of follow-up, 6 patients had 189 episodes of tachycardia successfully converted with AAI-T pacing, 4 patients had 8 episodes of tachycardia detected but not successfully converted, and 8 patients had no episodes of tachycardia with antibradycardia pacing alone. The number of patients receiving pharmacological therapy other than digoxin or beta blockade fell from 12 to 6. Two subjects died suddenly, 1 while wearing a Holter monitor. In both, tachycardia was detected and pace cardioversion attempted.
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Patients with asymptomatic AF were more often men and had less cardiac disease. During follow-up, in patients with asymptomatic AF, heart failure hospitalizations and severe adverse effects of antiarrhythmic and rate control drugs occurred significantly less frequently.
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In ten patients suffering from moderate to severe disturbances of liver function (hepatic cirrhosis, carcinomatous metastases of the liver) the elimination of 16-acetyl-gitoxin from plasma was measured after a single oral dose of 1.2 mg pengitoxin. In 9 of 10 patients the mean half-life amounted to 67.3 h (SD 14.2 h). In one patient with carcinomatous infiltration of the liver and concomitant cirrhosis, the half-life was prolonged to 165.3 h. The results point to an unchanged elimination of 16-acetyl-gitoxin in patients suffering from liver cirrhosis.
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The bioavailability of etoposide was 12.9 and 13.9% in monkeys and rats, respectively. Total body clearance of etoposide in monkeys was much less than hepatic blood flow, suggesting that the bioavailability would be limited at intestinal absorption. Marked vectorial transport of etoposide in the secretory direction was observed in rats, especially in the lower small intestine, and segmental differences were consistent with the distribution of P-gp expression. Vectorial transport was minimal in monkey small intestine. Our kinetic analysis indicated that P-gp contributes little to the intestinal permeability of etoposide and digoxin in monkeys, and apical uptake is rate-limiting.
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Certain basic (cationic) drugs are known to interact with the hepatic transport, and renal and/or biliary clearance of cardiac glycosides. The mechanisms behind these interactions are not fully understood. In the present study our aim was to investigate the effects of the two diastereomers, quinidine and quinine, as well as the calcium antagonist verapamil, on the hepatobiliary elimination of digoxin and ouabain in the isolated perfused rat liver.
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Proton pump inhibitor(PPI) is used for the treatment of peptic ulcer diseases for the following three purposes. Firstly, it is used to facilitate the ulcer healing and pain relief. Secondly, it is used for the eradication of H. pylori to minimize the recurrence of ulcer diseases. Thirdly, intravenous infusion of PPI is used for the hemostasis in patients with bleeding ulcers. Plasma concentration and acid suppressing effect of PPI are reported to be slightly augmented when standard doses of PPI are used in elderly cases. Since PPI is a safe drug and age-related increase in its plasma concentration is not remarkable, the dose adjustment of PPI may not be necessary even in elderly patients. Some PPIs are, however, reported to have metabolic interactions with other drugs such as diazepam and digoxin. Therefore drug interaction should be considered when the PPI is administered to the elderly with accompanying diseases.