No abstract available.
Mitral Valve* ; Quinidine*

Epilepsy of infancy with migrating focal seizure (MFEI) is an early-onset epileptic encephalopathy characterized by randomly migrating focal seizures and psychomotor deterioration. It is associated with mutations in a variety of genes, with potassium sodium-activated channel subfamily T member 1 (KCNT1) being an example. Previously reported KCNT1 mutations in MFEI are gain-of-function mutations. Therefore, quinidine therapy targeted at reduction of pathologically increased KCNT1 channel-mediated potassium conductance has been proposed as a target treatment for MEFI with KCNT1 mutation. The authors report a case involving a patient with MFEI and a missense mutation in KCNT1 (c.7129G>A; p.Phe346Leu) treated with quinidine therapy. Seizure activity was poorly responsive to quinidine.
Brain Diseases ; Epilepsy* ; Humans ; Mutation, Missense ; Potassium ; Quinidine* ; Seizures*

Since the standard recommendation by the International Contact Dermatitis Research Group, day 2 and day 4 patch test readings have been performed by most dermatologists. However, nearly half of positive reactions can be observed only either on day 2 or on day 4 and the interpretation of these reactions is a problem. We compared the patch test reaction according to the reading time in 754 patients who had been performed patch test with standard battery and in 367 patients who had been performed patch test with various cosmetic allergens including cosmetics as is. The study result is summoized as follows : 1. Persistent reactions were observed in 59.8% patients tested with standard battery, however transient reactions were observed in 20.8% and delayed reaction in 19.4%. 2. Frequent allergens which showed transient reaction were carba mix, paraben mix, tego, imidazolidinyl urea, in order of frequency. Frequent allergens which showed late reactions were neomycin sulfate, quinidine mix, farmaldehyde, and imidazolidinyl urea. 3. Persistent reactions were observed in 47.1% patients. tested with cosmetics as is, however transient reactions were observed in 29.4% and delayed reactions in 23.5%, Facial skin care products showed the i,.st high positivity. 4. Persistent reactions were observed in 41.0% patients tested with cosmetics ingredients, however transient reactions were observed in 38.7% and delayed reactions in 23.0%. Frequent cosmetic allergens were cinnamic alcohol, cinnamic aldehyde, ylang ylang oil, sandawood oil, and benzyl salicylate. In conclusion, the reaction pattern in general was similar to the dats of others. However, the individual allergens showed transient reaction were somewhat different. Higher rate of transient reactions were observed in patch test positive reactions with cosmetic ingredients than standard battery and cosmetics as is.
Allergens ; Cananga ; Dermatitis, Contact ; Humans ; Neomycin ; Patch Tests* ; Quinidine ; Reading ; Skin Care ; Urea

BACKGROUND: Quinidine appeared to increase serum digoxin levels when given with quinidine. Therefore elevated serum digoxin concentrations and clinical toxicity have been reported in patient receiving quinidine. Currently, Bayesian method which estimates the most probable parameters of the drug for each patient from population parameters data is useful approach for adjusting digoxin dosage. To increase the accuracy of Bayesian method, it is desirable to use population parameters of Korean. Therefore we evaluated the effect of quinidine on digoxin clearance in Korea. METHOD: Patient's records from 19 adult cardiac disease without CHF having normal renal and liver function from Seoul National University of Hospital respectively wre evaluated. Digoxin pharmacokinetic parameters, CL and Vd, were obtained from serum concentration of digoxin of single and combined therapy at each steady-state by using bayesian method. RESULTS: This study show that quinidine reduced the total body clearance of digoxin from 2.39+/-0.17 to 1.51+/-0.08ml/min/kg(p<0.05) and reduced the digoxin volume of distribution from 8.57+/-0.29 to 4.98+/-0.19L/kg(p<0.05). This results show that digoxin dosage reduced to 40-50% in Korean, if quinidine therapy is initiated.
Adult ; Bayes Theorem ; Digoxin* ; Drug Interactions ; Heart Diseases ; Humans ; Korea ; Liver ; Pharmacokinetics ; Quinidine* ; Seoul

BACKGROUND AND OBJECTIVES: Drug-induced electrocardiographic QT interval prolongation is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia, termed 'torsades de pointes' (TdP). Women are at greater risk for the development of drug-induced TdP. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening in young, healthy volunteers. SUBJECTS AND METHODS: Twelve women and 12 men each received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blinded, randomized crossover trial. Total plasma concentrations of quinidine were measured, and QT and corrected QT intervals were analyzed. RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (443.6+/-26.9 vs 402.1+/-31.3 msec, respectively, p=0.037). The mean value of the maximal DeltaQTc after quinidine infusion was higher in women (134.4+/-46.4 vs 117.5+/-37.7 msec, respectively, p=0.029), and the mean value of the minimal DeltaQTc for 1 hour after quinidine infusion was also higher in the female group (47.6+/-15.7 vs 83.7+/-25.4 msec, p=0.034). However, there were no significant differences in the time courses of the changes in the quinidine-induced QTc and DeltaQTc interval between the two groups (p=0.092, and p=0.305, respectively). CONCLUSION: Quinidine causes greater QT prolongation in women at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced TdP observed in women taking quinidine, and has implications for other cardiac and noncardiac drugs that prolong the QTc interval.
Asian Continental Ancestry Group ; Electrocardiography ; Female ; Healthy Volunteers ; Humans ; Incidence ; Male ; Plasma ; Quinidine ; Tachycardia, Ventricular

OBJECTIVEOn the basis that pinacidil can produce an "all or none" repolarization in right ventricular wall of canine, to observe the effects of quinidine on the marked transmural dispersion of repolarization. Recent studies have shown that ventricular myocardium is composed of at least 3 electrophysiological distinct cell types: epicardial, endocardial, and midcardial cells. Differences in the response of the 3 cell types to pharmacologic agents and/or pathophysiological states often result in amplification of intrinsic electrical heterogeneities, thus providing a substrate as well as a trigger for the development of arrhythmias. The study was designed to observe the right ventricular transmural heterogeneity in vitro canine heart tissue preparation level.

METHODSThe strips were isolated from the anterior wall of the right ventricular of canine. The preparations perfused with oxygenated (95%O(2)/5%CO(2)) Tyrode's solution. The tissues were stimulated at basic cycle lengths of 1000 ms. Standard microelectrode techniques were used. Transmembrane action potentials were recorded from epicardial, midcardial and endocardial cells respectively from right ventricular free wall of canine on different conditions [perusing with Tyrode's solution (Control), pinacidil (2.5 micromol/L), and quinidine (5 micromol/L) in turn].

RESULTSCompared with that of endocardial cells, the action potentials of canine ventricular epicardial and midcardial cells had more obvious spike and dome morphology. Pinacidil (2.5 micromol/L) caused a loss of the dome of transmembrane action potentials and a marked abbreviation of the action potential duration (APD) in right ventricular epicardial and midcardial cells, especially in epicardial cells, but not in endocardial cells (n = 10). With pinacidil (2.5 micromol/L), in epicardial cells, phase 2 amplitude of action potentials decreased from (117.7 +/- 9.3) mV to (71.3 +/- 6.4) mV (P < 0.01), and 90% of the APD(90) decreased from (198.2 +/- 20.8) ms to (103.9 +/- 13.5) ms (P < 0.01). The transmural dispersion of action potential duration increased from (48.5 +/- 9.2) ms to (128.7 +/- 13.5) ms (P < 0.01). Quinidine (5 micromol/L) effectively prolonged the APD abbreviated by pinacidil, restored or partly restored the dome of transmembrane action potentials of epicardial and midcardial cells but not of endocardial cells (n = 10). In epicardial cells phase 2 amplitude increased from (71.3 +/- 6.4) mV to (106.6 +/- 7.7) mV (P < 0.01), and 90% of the APD(90) increased from (103.9 +/- 13.5) ms to (185.9 +/- 15.7) ms (P < 0.01). The transmural dispersion of action potential duration significantly decreased from (128.7 +/- 13.5) ms to (54.3 +/- 10.8) ms (P < 0.01). Quinidine reduced pinacidil-induced transmural dispersion of phase 2 amplitude and the APD in right ventricular wall of canine.

CONCLUSIONBy restoring the dome and the APD of the epicardial and midcardial cells action potentials, quinidine (5 micromol/L) could reduce the marked transmural dispersion of repolarization caused by pinacidil.

Action Potentials ; drug effects ; Animals ; Dogs ; Heart Ventricles ; drug effects ; physiopathology ; Pinacidil ; pharmacology ; Quinidine ; pharmacology

Resistance of falciparum malaria to antimalarial agents is prevalent in many areas, whereas chloroquine-resistant vivax malaria has been reported mainly around New Guinea since 1989. Concomitant with the spread of chloroquine-resistant P. vivax and increase in number of international travelers, imported cases of chloroquine-resistant vivax malaria in travelers returning from these areas has been reported. We experienced a case of chloroquine resistance P. vivax infection imported from Mangole Island, Indonesia. Its origin is confirmed not to be indigenous by the gene encoding analysis for the polymorphic region of apical membrane antigen-1 in P. vivax. Gene sequencing of the P. vivax mdr1 gene revealed only one substitution located at the codon 1076 (F1076L). The case was managed with oral quinidine with successful outcomes.
Antimalarials ; Chloroquine ; Codon ; Indonesia ; Malaria ; Malaria, Vivax ; Membranes ; New Guinea ; Plasmodium ; Plasmodium vivax ; Quinidine

Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free Mg2+ ((Mg2+)i) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in (Mg2+)i would result in Mg2+ extrusion following hormonal stimulation. To determine the relation between Mg2+ efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, (Mg2+)i, ATP and Mg2+ content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. Mg2+ effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. Mg2+ effluxes induced by NE or cAMP were more stimulated in the presence of metabolic inhibitors (MI). Chemical hypoxia with NaCN (2 mM) caused a rapid decrease of cellular ATP within 1 min. Measurement of (Mg2+)i confirmed that ATP depletion was accompanied by an increase in (Mg2+)i. No change in Mg2+ efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced Mg2+ effluxes were inhibited by quinidine, imipramine, and removal of extracellular Na+. In addition, after several min of perfusion with Na+-free buffer, a large increase in Mg2+ efflux occurred when Na+-free buffer was switched to 120 mM Na+ containing buffer. A similar Mg2+ efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of Mg2+ effluxes by hormonal stimulation is directly dependent on intracellular Mg2+ contents and that these Mg2+ effluxes appear to occur through the Na+-dependent Na+/Mg2+ exchange system during chemical hypoxia.
Adenosine Triphosphate ; Animals ; Anoxia* ; Heart* ; Imipramine ; Magnesium* ; Muscle Cells* ; Norepinephrine ; Perfusion ; Quinidine ; Rats* ; Spectrophotometry

Nuedexta (dextromethorphan and quinidine) is an Food and Drug Administration approved medication for pseudobulbar affect. Interestingly, this drug was recently reported to improve speech, swallowing, and the ability to handle oral secretions along with emotional lability in amyotrophic lateral sclerosis (ALS) patients with bulbar symptoms. We report a Korean ALS patient whose bulbar function improved after administering Nuedexta for 6 months, extending therapeutic choice of approach in treating ALS patients.
Amyotrophic Lateral Sclerosis ; Deglutition ; Dextromethorphan ; Humans ; Quinidine ; United States Food and Drug Administration

Resistance of falciparum malaria to antimalarial agents is prevalent in many areas, whereas chloroquine-resistant vivax malaria has been reported mainly around New Guinea since 1989. Concomitant with the spread of chloroquine-resistant P. vivax and increase in number of international travelers, imported cases of chloroquine-resistant vivax malaria in travelers returning from these areas has been reported. We experienced a case of chloroquine resistance P. vivax infection imported from Mangole Island, Indonesia. Its origin is confirmed not to be indigenous by the gene encoding analysis for the polymorphic region of apical membrane antigen-1 in P. vivax. Gene sequencing of the P. vivax mdr1 gene revealed only one substitution located at the codon 1076 (F1076L). The case was managed with oral quinidine with successful outcomes.
Antimalarials ; Chloroquine ; Codon ; Indonesia ; Malaria ; Malaria, Vivax ; Membranes ; New Guinea ; Plasmodium ; Plasmodium vivax ; Quinidine