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In buccal cells, fluorescent PCR and FISH had similar reliability (94 and 93%) and accuracy (97 and 96%) rates. The reliability and accuracy of PRINS (91 and 25%) and conventional PCR (79 and 89%) were lower. In human blastomeres, FISH and fluorescent PCR had similar reliability (100%, 717; 95%, 190/201) rates. Accuracy rates were 71% (517) and 99% (188/190) for FISH and fluorescent PCR, respectively, however, too few blastomeres were analyzed by FISH for meaningful comparison. However, when these data are compared with published data, the method of choice for blastomere sexing appears to be fluorescent PCR.
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To elucidate the inhibited effect and regulated mechanism of IGFBp-1 on the carcinoma cells.
In this study, the combination of a thromboxane synthetase inhibitor (UK 38485) and a thromboxane receptor antagonist (ICI 185282) was tested for an interaction of potential therapeutic importance and the effect of acetylsalicylic acid pretreatment on this combination was evaluated in digoxin-induced arrhythmias in guinea-pigs. Drug treatments at the dose combinations used (ICI 185282: 0.2 mg/kg + 0.2 mg/kg/hr + UK 38485 0.1 mg/kg/hr and ICI 185282: 2 mg/kg + 2 mg/kg/hr + UK 38485 1 mg/kg/hr) markedly reduced the incidence of ventricular fibrillation, mortality rate and arrhythmia score. Pretreatment with acetylsalicylic acid plus drug combination resulted in a dose-dependent increase in mortality rate and arrhythmia score. The increase in mean arterial blood pressure, observed after digoxin administration, was inhibited by the combination therapy. Although heart rate values were increased, the computed pressure-rate index remained unchanged when compared with the control group. These data suggest that the combined treatment with a thromboxane synthetase inhibitor and a thromboxane receptor antagonist provides a better protection against digoxin intoxication than with either agent alone. Furthermore, the results illustrate that formation of cyclooxygenase metabolites of arachidonic acid plays an important role in this action.
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Postoperative JT is a transient arrhythmia that may be fatal after operation for congenital cardiac defects. Its precise cause is unknown. A variety of palliative treatments have evolved, but because of a low incidence of JT, large studies of the most efficient therapeutic sequence are lacking.
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This report describes the development of a method to measure mRNA in small samples of human tissue by the polymerase chain reaction with a nonradioactive label. In this method RNA is reverse-transcribed in the presence of a control RNA, and subsequently amplified by the polymerase chain reaction during which a nonradioactive label (digoxigenin-11-dUTP) is incorporated. Gel blotting and immunological detection of digoxigenin followed by a chemiluminescent reaction provide an intense signal on film. This allows the detection and quantitation of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase mRNA in 12 ng of RNA. We demonstrate that this is a sensitive and reproducible method, and that quantitation is linear with respect to the amount of mRNA present. The application of this method to the measurement of low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels in circulating peripheral blood mononuclear cells and human liver biopsy samples is discussed. The use of chemiluminescent reagents instead of radioactive labels allows this procedure to be performed safely in laboratories not equipped for radioactivity.
Hyperkalemia resulting from digoxin toxicity is a well-recognized phenomenon. We report a case in which hyperkalemia, bradycardia, and hypotension were unresponsive to standard therapy but appeared to respond to digoxin-specific antibodies (Fab). This case highlights the importance of a high index of suspicion for digoxin toxicity as a potential cause of refractory hyperkalemia.
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After 3 weeks of atrial fibrillation, domestic swine received atrioventricular nodal gene transfer with adenoviruses encoding beta-galactosidase (beta-gal), wild-type Galpha(i2) (wtGi), or constitutively active mutant (cGi). Heart rates in awake, alert animals were not altered by beta-gal or wtGi. cGi caused a sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with sedation. A tachycardia-induced cardiomyopathy was present before gene transfer. In the beta-gal group, cardiomyopathy worsened over time. In the wtGi group, the condition improved slightly, and in the cGi group, ejection fraction was near normal at the end of the study. TUNEL staining results corroborated this finding.
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Drug interactions common to all angiotensin-converting enzyme (ACE) inhibitors include those with thiazide diuretics and other antihypertensive agents. Interactions involving specific ACE inhibitors include captopril-digoxin, resulting in decreased clearance of digoxin from plasma in patients with heart failure, and captopril-probenecid, causing a decrease in captopril clearance. Tissue kinins, such as bradykinin, are metabolised by ACE inhibitors. Interactions involving bradykinin include captopril-indomethacin, in which an attenuation of the antihypertensive effects of captopril is manifest. Interestingly, neither enalapril nor lisinopril appear to show this interaction with indomethacin. Kinin-based interactions may also be important in the genesis of ACE inhibitor-induced cough and skin rash. Renal dysfunction affects the pharmacokinetics and pharmacodynamics of all ACE inhibitors, necessitating dosage reduction. Hepatic impairment is of less clinical importance, causing a delay in the onset of action of enalapril with initial doses, but probably having little relevance to long-term therapy.
Fundamental to the maintenance of ionic concentration gradients and transparency of the lens is the activity of Na+,K+-adenosine triphosphatase (ATPase) in the epithelial layer. Recent studies have identified endogenous digitalis-like compounds (DLCs) and 19-norbufalin and its peptide derivatives in human cataractous lenses. These compounds inhibit the activity of Na+,K+-ATPase and have been suggested to be involved in cataract formation. The present experiments were designed to test this hypothesis by determining the ability of digitalis and DLCs to induce changes in protein composition and leakage from rat lenses in organ culture.
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To determine gender differences in diagnostic workup and treatment of patients with heart failure.
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Fifty-four laboratories providing a serum digoxin monitoring service participated in a 16-month prospective quality control (QC) study that involved (a) determination of spiked QC samples based on a human serum matrix and (b) reanalysis by two to four reference laboratories of patient samples randomly selected among those assayed routinely. Interlaboratory variability on spiked samples was limited, coefficients of variation being usually in the 11-21% range. Correlations between values reported by individual reference laboratories on routine samples were reasonably good irrespective of the techniques used, which were the enzyme-multiplied immunoassay technique (EMIT) or the fluorescence polarization immunoassay (FPIA). When all data were considered, the correlation between the original routine values and reference results (r = 0.93) was comparable to that observed for the other analytes (phenytoin and theophylline) included in the survey. When subsets of results were evaluated according to the technique used, the agreement between routine and reference results was good for samples originally measured by FPIA (r = 0.96), moderate for samples originally measured by non-EMIT/non-FPIA techniques (r = 0.92), and poor for the few samples originally measured by EMIT (r = 0.55). The poor correlation with EMIT results could be ascribed largely to erratic performance of two individual laboratories. It is concluded that interlaboratory variability in routine drug measurements is greater for digoxin than for other analytes such as phenytoin and theophylline, and that the analytical performance of some laboratories is grossly inaccurate.
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During the last decades, the prevalence of allergy has increased worldwide. Allergic rhinitis ("hay fever") and asthma are two of the most common allergic diseases. A possible cause for increased allergy to pollen is air pollution. The increase of industrialization and the number of diesel engines associated with diesel exhaust particles (DEP) in the air parallel the increase in allergic airway diseases. To investigate the adjuvant effect of DEP in pollen allergy, Brown Norway (BN) rats were sensitized intranasally or intratracheally with timothy grass pollen (Phleum pratense) with or without DEP (3 mg/ml). Intranasal sensitization (200 microl, 10 mg/ml) was performed daily for 5 consecutive days and intratracheal sensitization (200 microl, 10 mg/ml) was performed once. Challenge with pollen was performed at day 21 similarly to the sensitization protocol. Blood samples were taken at day 28 after the first sensitization. The binding of DEP to pollen grains was studied by scanning electron microscopy and the inflammatory response in the lung was studied by light microscopy. Immunoglobulin E (IgE) and IgG(1) responses against pollen grains were measured by digoxigenin (DIG) enzyme-linked immunosorbent assay (ELISA). Scanning electron microscopy revealed a mixture of free DEP and DEP associated with pollen grains. Both intranasal and intratracheal routes of administration of pollen grains induced inflammatory reactions in the lung with an influx of macrophages, eosinophilic granulocytes, and granuloma formation. Pollen grains were localized in the alveoli after both intranasal and intratracheal administration and were surrounded by macrophages. The number and localization of pollen grains were similar for both routes of administration. After coexposure with DEP, DEP-loaded macrophages were found around the pollen. Localization, inflammatory reaction, and integrity of pollen were similar to those seen without DEP. At day 28, specific IgE and IgG(1) antibodies were found in serum of rats immunized intranasally or intratracheally. IgE antibody response was higher in rats immunized with pollen grains and DEP than in rats immunized with pollen only (dilution mean +/- SEM: 59.4 +/- 4.6 vs. 27 +/- 5.1). The IgG(1) antibody response was much higher compared to the IgE response (factor of 10(4)), but the level of IgG(1) antibodies was only slightly increased by DEP (dilution mean +/- SEM: 24.2 +/- 2.0 x 10(4) vs. 16.1 +/- 2.1 x 10(4)). In conclusion, the intranasal application of pollen in the BN rat is a suitable and elegant method to evoke inflammatory reactions in the lung and pollen-specific IgE responses measured by DIG ELISA. Finally, this model gives similar results on adjuvant activity of DEP found in the ovalbumin models presented previously.
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Two patients had potentially serious drug interactions (phenytoin, digoxin) that were probably attributable to changes in pharmacokinetics and pharmacodynamics caused by high-dose calcium channel blocker therapy (diltiazem) in the treatment of pulmonary hypertension. Even in the approved normal dosages for the treatment of angina and hypertension, calcium channel blockers are known to cause significant changes in the metabolism of other drugs. Currently, no data exist on the effects of the very high dosages of these drugs, administered to patients with pulmonary hypertension, on the metabolism and clearance of other agents, although, based on our experience and literature reports, recommendations for monitoring therapy can be made.
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Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types.
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Polypharmacy is associated with increased mortality in NH residents with advanced cognitive impairment at the end of life.
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MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.
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The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. beta-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents--all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).
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The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions.
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No significant variation was observed in the clinical variables analysed. The shortening and ejection fraction, the mean dP/dt and stroke volume significantly increased and the wall stress index of left ventricle, the meridional left ventricular end systolic wall stress and the mitral regurgitation jet area decreased in the phases with medication as compared with that in the placebo phase.
In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07μM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study.
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Idiopathic dilated cardiomyopathy may rarely present in pregnancy. A multidisciplinary approach and close peripartum monitoring are important in management and termination of pregnancy should be considered. Thromboembolic complications are a major risk.
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Recent research has demonstrated the presence of endogenous compounds in blood and urine that crossreact with antibodies raised against digoxin. Given the widespread therapeutic use of digoxin and its being monitored clinically by immunoassay, such digoxin-like immunoreactive compounds pose significant diagnostic and interpretive problems. Serum levels of this factor(s) approaching therapeutic digoxin levels have been found in digoxin-free patients in renal failure, pregnant women, and newborns. The compound is incompletely characterized; however, existing data suggest that it is a small, neutral, nonpeptidic compound. In serum it is highly protein bound, and alterations in this binding appear to give rise to the false-positive assay results. The urinary form is probably conjugated. Digoxin-like immunoreactive substances may play a role in volume homeostasis and appear associated with essential and pregnancy-induced hypertension. If such roles are primary, measurement of digoxin-like immunoreactive substances may prove to be of value in and of itself.
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Nine patients on enalapril and 12 on digoxin improved their functional capacity. Digoxin improved exercise time in 76 +/- 168 sec (p = 0.022), whereas this change was not significant with enalapril (38 +/- 158 sec; p = 0.2). With enalapril treatment, ventricular diastolic dimension decreased from 59.3 +/- 8.1 to 58 +/- 9.3 mm and the area of mitral insufficiency decreased from 8.1 +/- 3.5 to 6.6 +/- 3.1 cm2. Digoxin did not induce any significant echocardiographic change.
The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median C(max) reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed.
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A large-scale, prospective, 8-week, office-based study was conducted to evaluate the effects of adding captopril to a therapeutic regimen of diuretic and digoxin or diuretic alone in the management of patients with mild to moderate congestive heart failure (CHF). A total of 2218 primary care physicians evaluated 6669 patients over the study period for efficacy parameters, which included changes in a modified New York Heart Association (NYHA) functional classification, symptomatology, and daily activity levels. Overall, 63.8% of evaluated patients improved with regard to functional ability, with 19% improving two or more modified NYHA classes. Symptoms of CHF, including dyspnea on exertion, fatigue, and orthopnea and signs, including rales and peripheral edema, were reduced in 86% of these patients: 41.5% demonstrated mild improvement; 30.0%, moderate improvement; and 14.5%, marked improvement. Three parameters, with which patients reported having difficulty at study entry, were assessed serially to evaluate changes in functional capacity; 78.5% of patients reported an increased walking distance, 72.3% had increased capacity for climbing stairs, and 60.2% had improved capacity for individual recreational activities. Adverse experiences were reported in 18.1% of all patients; 4.9% of patients withdrew from the study because of an adverse effect. Combination therapy with captopril and diuretic for CHF was shown to be safe and effective regardless of patient age (less than 70 years vs. greater than or equal to 70 years), duration of heart failure (less than 1 year vs. greater than 1 year), presence of digoxin treatment, or the dosing schedule employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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Patients admitted to medical departments with HF are different to those found in clinical trials. Their management is currently suboptimal. Differences in treatment between internists and cardiologists appear to be accounted for by differences in the patients they treat.
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An effective management and evidence-based integrated therapeutic approach progressively and significantly improved the long-term prognosis of IDCM during the last three decades.