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1.
Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: are calcium channel blockers superior to digoxin for controlling the ventricular rate in patients with acute atrial fibrillation?
Parris, RJ, Clarke, SF
Emergency medicine journal : EMJ. 2009;(12):881-3
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2.
Verapamil versus digoxin and acute versus routine serial cardioversion for the improvement of rhythm control for persistent atrial fibrillation.
Hemels, ME, Van Noord, T, Crijns, HJ, Van Veldhuisen, DJ, Veeger, NJ, Bosker, HA, Wiesfeld, AC, Van den Berg, MP, Ranchor, AV, Van Gelder, IC
Journal of the American College of Cardiology. 2006;(5):1001-9
Abstract
OBJECTIVES The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF. BACKGROUND Rhythm control is desirable in patients suffering from symptomatic AF. METHODS A total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 x 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months. RESULTS At baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02). CONCLUSIONS An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy.
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3.
Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin.
Mueller, SC, Uehleke, B, Woehling, H, Petzsch, M, Majcher-Peszynska, J, Hehl, EM, Sievers, H, Frank, B, Riethling, AK, Drewelow, B
Clinical pharmacology and therapeutics. 2004;(6):546-57
Abstract
BACKGROUND AND OBJECTIVE St John's wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin. METHODS A randomized, placebo-controlled, parallel-group study was performed in 96 healthy volunteers in 3 study parts. A 7-day loading phase with digoxin was followed by 14 days of comedication with placebo or one of 10 St John's wort products varying in dose and formulation. The pharmacokinetics of digoxin was determined before comedication and on day 14 of comedication. RESULTS Comedication comprised traditionally used Hypericum products; 2 g powder without hyperforin, tea, juice, oil extract, and placebo had no significant interaction with digoxin nor did hyperforin-free extract (Ze 117) or low daily doses of hyperforin-containing Hypericum powder (1 g, 0.5 g). However, comedication with the high-dose hyperforin-rich extract LI 160 resulted in a reduction of digoxin area under the curve from time 0 to 24 hours (AUC(0-24)) of -24.8% (95% confidence interval [CI], -28.3 to -21.3), a reduction in digoxin maximal plasma concentration (C(max)) of -37% (95% CI, -42 to -32), and a reduction in digoxin plasma concentration at 24 hours after previous dosing (C(trough)) of -19% (95% CI, -27 to -11). Comedication with 4 g Hypericum powder with comparable hyperforin content resulted in a reduction in digoxin AUC(0-24) of -26.6% (95% CI, -37.3 to -15.9), a reduction in digoxin C(max) of -38% (95% CI, -48 to -18), and a reduction in digoxin C(trough) of -19% (95% CI, -27 to -10). Two grams of Hypericum powder with half the hyperforin content resulted in a less prominent reduction in AUC(0-24) of -17.7% (95% CI, -21.6 to -13.7), C(max) (-21%; 95% CI, -40 to -2), and C(trough) (-13%; 95% CI, -21 to -5). CONCLUSIONS The interaction of St John's wort and digoxin varies within St John's wort preparations and doses and seems to be correlated with the dose, particularly of hyperforin.
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4.
Cross-sectional study of heart failure therapy with angiotensin converting enzyme inhibitors and digoxin.
Mahmood, SA, Hussein, GM, Hamza, EA
Saudi medical journal. 2004;(8):1060-5
Abstract
OBJECTIVE The aim of the present study is to show a better short-term (2 weeks) clinical improvement in patients with heart failure (HF) who are receiving angiotensin converting enzyme inhibitors (ACEIs) (with or without digoxin) when compared to the standard therapy excluding ACEIs. METHODS The study was conducted in Al-Gamhuria Teaching Hospital, Aden, Yemen, from January to July 2003. In this study, 78 patients with HF were enrolled into 3 therapeutic groups (ACEIs alone, ACEI and digoxin and digoxin alone) and their responses within 2 weeks were recorded. Exclusion criteria were as follows: thyroid disorders, gastrointestinal disturbances (diarrhea, malabsorption), electrolyte unbalanced (unless corrected) and insufficient data. Serum creatinine was measured at the beginning and after 10 days. In addition, the patients' body weight and age were recorded. Criteria for a complete improvement within 2 weeks were the occurrence of the following: 1) The relief of pulmonary congestion, 2) Decrement in heart rate to less than 74 +/- 5, 3) Disappearance of the lower limb edema, and 5) Recorded positive electroencephalogram change. Partial amelioration was recognized if only 2 or 3 of the preceding criteria were observed. RESULTS Nine patients received digoxin alone, while 40 patients were treated with ACEIs and digoxin. Treatment with ACEIs without digoxin was observed in 29 patients. The discrepancy between the number of patients was necessitated by the need of patients with HF. This last category of treatment regimen produced better clinical improvement (complete with 10.1%, partial with 24.3%) compared to the digoxin group without ACEI (complete 2.5% or partial 5.1%). Nevertheless, the addition of digoxin to an ACEI increased this ratio (17.8% for complete and 28.2% for partial improvement). A 49.3% increase in serum creatinine was observed after 10 days in 25 HF patients, who were randomly selected and followed up (the baseline concentration was 99.75 +/- 9.9 umol/L, while the level after 10 days was 148.97 +/- 19.8 umol/L, p=0.005). CONCLUSION We confirmed that short-term use of ACEI regimens has a superior effect on the therapy of HF (34.4% complete and partial response) as compared to the therapy of not using ACEI (7.6% had a complete and partial response). The combination of ACEI and digoxin has resulted in the best outcome (46% had a complete and partial response). However, we also noticed a significant rise in serum creatinine by 49% concomitant with the use of ACEI (the baseline concentration was 99.75 +/- 9.9 um/L, while the level after 10 days was 148.97 +/- 19.8 umol/L, p=0.005).
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5.
Hypothalamic digoxin, hemispheric chemical dominance, and creativity.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(4):565-77
Abstract
The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.
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6.
Hypothalamic digoxin, regulation of neuronal transmission, and cerebral dominance.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(6):821-30
Abstract
The present study assessed the neurochemical differences between right hemispheric dominant and left hemispheric dominant individuals. The HMG CoA reductase activity, serum digoxin, magnesium, tryptophan catabolites, tyrosine catabolites, and RBC membrane (Na+)-K+ ATPase activity were measured in individuals of differing hemispheric dominance. The results showed that right hemispheric dominant individuals had elevated digoxin synthesis, increased tryptophan catabolites, and reduced tyrosine catabolites and membrane (Na+)-K+ ATPase with hypomagnesemia. Left hemispheric dominant individuals had the opposite patterns. Right hemispheric dominance represents a hyperdigoxinemic state with membrane sodium-potassium ATPase inhibition. Left hemispheric dominance represents the reverse pattern with hypodigoxinemia and membrane sodium-potassium ATPase stimulation.
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7.
Hypothalamic-mediated model for Creutzfeldt-Jakob disease: relation to hemispheric chemical dominance.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(7):971-87
Abstract
The isoprenoid pathway including endogenous digoxin was assessed in Creutzfeldt-Jakob Disease (CJD). This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with CJD and in those with right hemispheric chemical dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glyco conjugates reduced. On the other hand, in patients with left hemispheric chemical dominance, the reverse patterns were obtained. The role of the isoprenoid pathway in the pathogenesis of CJD and its relation to hemispheric chemical dominance is discussed.
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8.
Hypothalamic digoxin and hemispheric chemical dominance: relation to speech and language dysfunction.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(6):797-814
Abstract
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. Since endogenous digoxin can regulate neurotransmitter transport and dolichols can modulate glycoconjugate synthesis important in synaptic connectivity, the pathway was assessed in patients with dyslexia, delayed recovery from global aphasia consequent to a dominant hemispheric thrombotic infarct, and developmental delay of speech milestone. The pathway was also studied in right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of speech disorders. The plasma/serum--activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone--and tryptophan/tyrosine catabolic patterns, as well as RBC (Na+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism and membrane composition was also studied. The study showed that in dyslexia, developmental delay of speech milestone, and delayed recovery from global aphasia there was an upregulated isoprenoidal pathway with increased digoxin and dolichol levels. The membrane (Na+)-K+ ATPase activity, serum magnesium and ubiquinone levels were low. The tryptophan catabolites were increased and the tyrosine catabolites including dopamine decreased in the serum contributing to a speech dysfunction. There was an increase in carbohydrate residues of glycoproteins, glycosaminoglycans, and glycolipids levels as well as an increased activity of GAG degrading enzymes and glyco hydrolases in the serum. The cholesterol:phospholipid ratio of RBC membrane increased and membrane glycoconjugates showed a decrease. All of these could contribute to altered synaptic inactivity in these disorders. The patterns correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance may play a role in the genesis of these disorders. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.
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9.
Hypothalamic digoxin, cerebral chemical dominance, and calcium/magnesium metabolism.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(7):999-1004
Abstract
The study assessed the biochemical differences between right hemispheric dominant and left hemispheric dominant individuals. The HMG CoA reductase activity, isoprenoid metabolites--serum digoxin--serum magnesium, and RBC membrane Na+-K+ ATPase activity were also studied. The results showed that right hemispheric chemically dominant individuals had increased (i) HMG CoA reductase activity, elevated digoxin levels, (ii) reduced RBC membrane Na+-K+ ATPase activity and serum magnesium levels. Left hemispheric chemically dominant individuals had the opposite patterns. Right hemispheric chemical dominance represents a hyperdigoxinemic/hypomagnesemic state with membrane sodium-potassium ATPase inhibition. Left hemispheric chemical dominance represents the reverse pattern with hypodigoxinemia/hypermagnesemia and membrane sodium-potassium ATPase stimulation. Cerebral chemical dominance can regulate calcium/magnesium metabolism.
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10.
The concept of cerebral chemical dominance.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(7):957-70
Abstract
The study assessed the biochemical differences between right hemispheric dominant and left hemispheric dominant individuals detected by handedness and the dichotic listening test. The isoprenoid metabolites--digoxin, dolichol, and ubiquinone, glycoconjugate metabolism, free radical metabolism, and the RBC membrane composition were studied in individuals with differing hemispheric dominance. The results showed that all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals had increased HMG CoA reductase activity, elevated digoxin and dolichol levels. The serum magnesium, RBC membrane Na+-K+ ATPase activity and serum ubiquinone levels were reduced in all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals. The tryptophan-derived neurotransmitters--serotonin, quinolinic acid, strychnine, and nicotine--were increased while the tyrosine derived neurotransmitters--dopamine, noradrenaline, and morphine--were reduced in all right hemispheric dominant individuals and 50% of left hemispheric dominant individuals. The other 50% of left hemispheric dominant individuals had decreased HMG CoA reductase activity, reduced digoxin, and dolichol levels. The serum magnesium, RBC membrane Na+-K+ ATPase activity, and serum ubiquinone levels were increased in this group. The tryptophan derived neurotransmitters--serotonin, quinolinic acid, strychnine, and nicotine were reduced, while the tyrosine-derived neurotransmitters--dopamine, noradrenaline, and morphine-- were increased in the rest (50% of left hemispheric dominant individuals). Hemispheric dominance detected by the dichotic listening test and handedness has no correlation with cerebral chemical dominance.