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Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.v. at 1,180 +/- 340 micrograms (15 micrograms/kg) over two hours. After 24 hours, IN was given p.o. at 231 +/- 44 micrograms. The time course effect of IN i.v. revealed an increase in cardiac index and a decrease in pulmonary capillary wedge pressure and blood pressure. Daily oral administration of IN or placebo was carried out for up to 3 months. There were no significant hemodynamic changes of chronically administered IN. The maximum oxygen uptake increased in placebo relative to IN therapy. IN tended to be arrhythmogenic as evidenced by a general increased frequency of ventricular premature contractions of both single and paired type. Therefore, IN had some hemodynamic efficacy on acute i.v. and p.o. administration but not during chronic therapy, and there was negative safety features of arrhythmias.
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The accumulation of 99mTc(V)-DMSA in bilateral breasts was recognized in a 60-year-old male with drug-induced gynecomastia. There are some reports describing 99mTc(V)-DMSA accumulation in normal female breast, fibrous dysplasia of the breast and metastatic lesions of breast carcinoma, but to my knowledge, there have been no reports describing 99mTc(V)-DMSA accumulation in gynecomastia.
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The newly developed model provided good predictive performance of serum digoxin level. Taking simplicity in practical use into account, the clinical application of the proposed model will allow for accurate and rapid determination of the initial maintenance dosing regimen of digoxin based on the individual Ccr value, without actual measurement of its serum concentration.
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Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.
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We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications.
During follow-up (2.3 +/- 0.6 years), a significant difference between both groups in heart rate was observed (72 +/- 5 vs 90 +/- 8 beat/min; P < .001). Rate control drugs were not significantly different between both groups. New York Heart Association class and fractional shortening remained unchanged in both groups. There were 17 (23%) end points in the low heart rate group and 24 (17%) in the higher heart rate group (absolute difference, 5.4 [-7.3 to 8.2]; P = ns). Independent predictors for the primary end point were coronary artery disease, digoxin use, and interrupted anticoagulation, not high heart rate. Quality of life was comparable in both groups during follow-up.
Serum digoxin measurement is often performed in medical laboratories. A professional association specialized in quality control, based in Lyon, has been organizing punctual controls of medication measurement for the past ten years. The results are analysed in term of intra and inter-technique precision, difference between methods and specificity in regard to endogenous or exogenous interfering substances. Methods have changed with a quasi disappearance of the methods used ten years ago (FPIA, EMIT) and introduction of new technologies on recent immunoanalysis automates. The results observed with the different instruments are similar. Reproductibility has not changed over ten years. Some difficulties remain in the measurement of low concentrations of digoxin. Many substances interfere in digoxin measurement : digoxigenine (inactive metabolite), endogenous digoxin-like immunoreactive factors, spironolacton, antidigoxin antibodies used for treatment of digitalic intoxications. These interferences depend on the method which is used, but it is essential to know them in order to interpret the results correctly.
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Large, nationwide United States commercial insurance database.
Using a multilumen perfusion catheter, we investigated the impact of P-glycoprotein inhibition on absorption of two compounds: the P-glycoprotein substrate digoxin and the marker for passive transcellular absorption antipyrine. Two 20cm adjacent jejunal segments were isolated with the multilumen perfusion catheter in seven healthy subjects. Unlabelled and deuterated digoxin and antipyrine, respectively, were simultaneously infused into either of the intestinal segments. One of the segments was additionally perfused with the P-glycoprotein inhibitor quinidine. Intestinal perfusates were collected for 3 hours, and drug concentrations were determined in the intestinal perfusates, plasma and urine.
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Accounting for the marked increase in polypharmacy, prescribing quality appears to have improved with a reduction in the odds of having PIP from 1997 to 2012. With growing numbers of people taking multiple regular medicines, strategies to address the related challenges of polypharmacy and PIP are needed.
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RNA in situ hybridization using digoxigenin-labeled riboprobes on tissue sections is a powerful technique for revealing microscopic spatial gene expression. Here, we describe an in situ hybridization method commonly practiced in Arabidopsis research labs. The highly stringent hybridization condition eliminates the usage of Ribonlucease A and gives highly specific signals. This also allows the use of longer probes which enhance signal strength without cross hybridization to closely related genes. In addition, using spin columns in template and riboprobe purification greatly reduces background signals.
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Potential pharmacokinetic interactions between 20 mg dapagliflozin, 40 mg simvastatin, or 320 mg valsartan were assessed in an open-label, randomized, five-period, five-treatment, unbalanced crossover study in 24 healthy subjects. In a second study, the effects of steady-state dapagliflozin on the pharmacokinetics of 25 mg warfarin or 0.25 mg digoxin were assessed in an open-label, randomized, two-period, two-treatment crossover study in 30 healthy subjects divided into two cohorts. The potential pharmacodynamic interaction between dapagliflozin and warfarin was also evaluated.
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Rats were randomly assigned into DIG, low dose-BBR, middle dose-BBR and high dose-BBR group. After singe or a 2-week ig pretreatment with BBR, serum DIG concentration was determined by radioimmunoassay. Pharmacokinetic calculations were performed on each individual set of data using 3P97 practical pharmacokinetic software.
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Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is approved for use as adjunctive therapy in adult patients with partial onset seizures. Oral levetiracetam 1000, 2000 and 3000 mg/day administered as adjunctive therapy for up to 18 weeks significantly increased responder rates and reduced seizure frequency compared with placebo in 3 well designed pivotal trials in adults with treatment-refractory partial seizures with or without secondary generalisation. Levetiracetam 3000 mg/day also significantly increased the number of seizure-free patients, but the effects of levetiracetam 1000 and 2000 mg/day on this end-point were unclear. Effects on seizure severity were not assessed in these trials. Although not yet approved as monotherapy or for use in paediatric patients, efficacy was observed with levetiracetam 3000 mg/day as monotherapy in adult patients with refractory partial seizures with or without secondary generalisation and with the 10 to 40 mg/kg/day dosage as adjunctive therapy in children with refractory partial seizures. However, these data are limited. Oral levetiracetam 1000, 2000 and 3000 mg/day as adjunctive therapy is generally well tolerated with an overall incidence of adverse events similar to that observed with placebo. The most commonly reported events in individual clinical trials were CNS-related and included somnolence, asthenia, headache and dizziness. Levetiracetam administered as adjunctive therapy does not appear to interact with other anticonvulsant drugs, and no clinically relevant interactions were observed between levetiracetam and digoxin, warfarin or probenecid; oral contraceptive protective efficacy was also not affected by levetiracetam.
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We describe, to the best of our knowledge for the first time, the occurrence of idiopathic atrial flutter (AF) in two male children of a family. The two brothers are the third and sixth of seven children, and the only males. The parents do not suffer from any heart disease. The first sister died in Turkey at the age of twenty days. The parents do not know the cause of death. The fourth sister died at de age of five years, also in Turkey, probably because of meningitis. Electrocardiograms of the parents and the other three sisters are normal. Besides the unique familial occurrence, the AF themselves offer some unusual features. In the first patient, the AF could not be converted to sinus rhythm. In the second patient, the AF occurred paroxysmally, and in addition to the AF, the electrocardiogram tracings revealed paroxysmal atrial tachycardia.
Thirteen patients (4.3%) had an arrhythmic event (sudden death in 11, sustained ventricular tachyarrhythmia in 2). The 25-Hz high pass filtered signal-averaged ECG at discharge was 64% sensitive (95% confidence intervals [CI] 36% to 92%) and 81% specific (95% CI 76% to 86%). High grade ventricular ectopic activity on the Holter ECG was only 38% sensitive (95% CI 12% to 64%) and 74% specific (95% CI 71% to 77%). Left ventricular ejection fraction < 0.4 was the best test for prediction of arrhythmic events (sensitivity 75% [95% CI 50% to 100%] and specificity 81% [95% CI 76% to 85%]). In multivariate analysis, in rank order, digoxin therapy at discharge, an abnormal 25-Hz signal-averaged ECG before discharge, absence of angina before index infarction and previous infarction were predictive of arrhythmic events. With digoxin therapy excluded, ejection fraction was an independent predictor. Discriminant analysis identified a high risk group (12% of the study patients) with an event rate of 26%.
Phage display has been used extensively in antibody (Ab) engineering. Sometimes, however, phage display vectors exhibit deletion of immunoglobulin (Ig) genes. As an approach to circumvent the recombination-deletion of the murine anti-digoxin Fab 40-50 cloned into the pComb3 vector, the vector was modified with short synthetic oligonucleotides by replacing a pelB leader sequence with a gene 3 (g3) leader sequence and by using a single lacZ promoter sequence. By this means, the N-terminal amino acids of the L chain and Fd remained unchanged, and a random HCDR3 library built on this newly designed vector did not exhibit the recombination-deletion.
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The Optopatch platform provides a robust assay to measure APs and CTs in hiPSC-CMs. This addresses the CiPA mandate and will facilitate comparisons of cell-based assays to human clinical data.
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prescribing in nursing homes is frequently suboptimal. Indicators to measure prescribing quality, including appropriateness of prescribing certain drugs or combinations of drugs, to hospital inpatients have been developed previously.
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The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.
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Among them, 16 cases (53.3%) were positive for HPV 6/11 DNA. None of cases of SCP were positive for HPV 16/18 DNA.
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The present era of medicine is concerned to a large measure with cost containment and the advent of managed care. For these reasons the concept of reducing hospital stays with a concomitant reduction in hospital cost is very attractive. The role of fast track is to ensure that we are not placing the patient at any additional risk and in fact are improving recovery and patient well-being.
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An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.
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All observed UDRs among a total of 4032 in-patients were recorded on a simple registration form, filled in by doctors assigned to collect the information, which was then analysed in cooperation with the Drug Commission of the German Medical Council (AKdA).
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After undergoing a splenorenal shunt the patient made a good recovery. However, she later developed pulmonary hypertension and died after undergoing a hysterectomy and a bilateral salpingo-oophorectomy.
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MicroRNAs (miRNAs) are endogenous approximately 22 nucleotide RNAs that play critical roles in many cellular processes including cell differentiation, proliferation, and apoptosis. The analysis of spatiotemporal expression of miRNAs is important for dissecting their roles in development and during physiological/pathophysiological processes. In situ hybridization is a powerful technology that allows cellular localization. However, the detection of miRNAs by in situ hybridization has been challenging because of the low affinity of conventional RNA or DNA probes due to the small sizes of miRNAs. Here, we describe a protocol for miRNA in situ hybridization on mouse tissue cryosections using locked nucleic acid (LNA) probes. LNA probes demonstrate a much higher affinity to their complimentary RNAs compared to conventional RNA and DNA oligo probes, which allow detection of miRNAs in tissue sections with excellent specificity.