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The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents.

DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of gliomas. Despite their frequent use, the therapeutic efficacy of these agents is limited by the development of resistance. Previous studies suggest that the mechanism of this resistance is complex and involves multiple DNA repair pathways. To better define the pathways contributing to the mechanisms underlying glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose- and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci formation, both hallmarks of FA pathway activation. The FA-deficient cells were more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To test whether these observations were pertinent to glioma biology, we screened a panel of glioma cell lines and identified one (HT16) that was deficient in the FA repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA pathway activation by a small molecule inhibitor (curcumin) or by small interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87 glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive to that of methyl-guanine methyl transferase inhibition. The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance.

Antineoplastic Agents, Alkylating↗

Pathway length and evolutionary constraint in amino acid biosynthesis.

The evolutionary properties of a metabolic network may be determined by the topology of the network. One attribute of pathways that make up the network is the number of enzymatic steps between initial substrates and final products. To determine the effect of pathway length on evolutionary lability of pathway structure, we examined amino acid biosynthetic pathways across 48 sequenced organisms. We demonstrate that longer pathways exhibit lower rates of change in pathway structure than shorter pathways. This finding suggests that increasing complexity may increase constraint on evolutionary change.

Amino Acids↗

Methionine biosynthesis and its regulation in Corynebacterium glutamicum: parallel pathways of transsulfuration and direct sulfhydrylation.

There are two alternative pathways leading to methionine synthesis in microorganisms: The transsulfuration pathway involves cystathionine as the intermediate and utilizes cysteine as the sulfur source, but the direct sulfhydrylation pathway bypasses cystathionine and uses inorganic sulfur instead. While most microorganisms synthesize methionine via either one of these pathways, Corynebacterium glutamicum utilizes both pathways, which appear to be fully functional. In C. glutamicum, each pathway is catalyzed by independent enzymes and is tightly regulated by methionine. Although the physiological significance of parallel pathways remains to be elucidated, their presence suggests metabolic flexibility and efficient adaptation of the organism to its environment.

Carbon-Oxygen Lyases↗

Metabolic pathway structures for recombinant protein synthesis in Escherichia coli.

Escherichia coli is a valuable commercial host for the production of heterologous proteins. We used elementary mode analysis to identify all possible genetically independent pathways for the production of three specific recombinant proteins, green fluorescent protein, savinase and an artificial protein consisting of repeating units of a five-amino-acid cassette. Analysis of these pathways led to the identification of the most efficient pathways for the production of each of these proteins. The results indicate that the amino acid composition of expressed proteins has a profound effect on the number and identity of possible pathways for the production of these proteins. We show that several groups of elementary modes produce the same ratio of biomass and recombinant protein. The pattern of occurrence of these modes is dependent on the amino acid composition of the specific foreign protein produced. These pathways are formed as systemic combinations of other pathways that produce biomass or foreign protein alone after the elimination of fluxes in specific internal reversible reactions or the reversible carbon dioxide exchange reaction. Since these modes represent pathway options that enable the cell to produce biomass and protein without utilizing these reactions, removal of these reactions would constrain the cells to utilize these modes for producing biomass and foreign protein at constant ratios.

Algorithms↗

Topographical analysis of lymphatic pathways from the meso- and hypopharynx based on minute cadaveric dissections: possible application to neck dissection in pharyngeal cancer surgery.

To facilitate the development of new operative procedures for pharyngeal cancer, it is important to understand the precise location of the lymph nodes and their pathways. Minute dissection of 22 neck-halves (11 adult cadavers) was undertaken to determine the location and topographical relationships of the lymphatics of the pharynx. Four groups of lymph nodes on the drainage pathways from the meso- and hypopharynx to the internal jugular nodes were classified according to their topographical relationships to the carotid arteries: lateral pharyngeal, superior thyroid, lateral retropharyngeal and medial retropharyngeal nodes. Lymphatics from the mesopharynx passed laterally to lateral pharyngeal or jugulodigastric nodes or slightly upward to lateral retropharyngeal nodes. Lymphatic drainage from the hypopharynx was multidirectional with the pathways being classified as follows: ascending pathway to the lateral pharyngeal and lateral retropharyngeal nodes, lateral pathway to the internal jugular chain, and descending pathway connecting to the uppermost vessels ascending from the recurrent laryngeal nerve chain. In addition, a contralateral pathway was found originating from the hypopharynx extending to the contralateral internal jugular chain. These findings provide valuable information for comparison with CT and MRI studies, as well as with clinicopathological data, to clarify the precise mode of metastasis in head and neck cancers. These results are also applicable to neck dissection in meso- and hypopharyngeal cancers.

Aged↗

UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae.

The Ubc13 protein was recently identified for its unique role in ubiquitin (Ub) chain assembly at the Ub Lys-63 residue instead of the conventional Lys-48 residue. This activity requires Ubc13 to form a complex with Mms2 and indeed ubc13 and mms2 mutations have been shown elsewhere to be epistatic with respect to UV sensitivity. The MMS2 gene is known to be a member of the error-free DNA postreplication repair (PRR) pathway. By contrast, the Ub Lys-63 residue has been previously implicated in the error-prone PRR pathway, since yeast cells carrying the ubiK63R mutation are defective in UV-induced mutagenesis. In the present study, we attempted to define the role of UBC13 within the PRR pathway. We found that the ubc13 mutation is epistatic to mms2 and rad6, confirming that UBC13 belongs to the PRR-pathway. We also found that ubc13 is synergistic to the error-prone PRR pathway mutation rev3, indicating that UBC13 is in a pathway alternative to REV3 mutagenesis. The ubc13 mutant displays up to a 30-fold increase in the spontaneous mutation rate, and this increase is largely REV3 dependent. In addition, UV-induced mutagenesis is fully functional in the ubc13 mutant. These results together demonstrate that UBC13 is a member of the error-free PRR pathway. The involvement of UBC13 in cellular tolerance to DNA-damage is further implicated by our finding that the UBC13 transcript level is increased up to 6-fold in response to DNA-damage.

Blotting, Northern↗

Slow pathway ablation in children with documented reentrant supraventricular tachycardia not inducible during invasive electrophysiologic study.

UNLABELLED: Radiofrequency catheter ablation (RFA) has become the procedure of choice for permanent therapy of atrioventricular nodal reentrant tachycardia (AVNRT). This report presents our experience with atrio-ventricular node (AVN) modification in patients with documented narrow complex reentrant SVT, but no evidence for an accessory pathway, and no inducible tachyarrhythmia during invasive electrophysiology (EP) study. METHODS: The study population consists of nine children, age range 6-13 years (median 9) with previously documented SVT who had no tachyarrhythmia inducible during EP study (at baseline and following isoprenaline infusion). Eight of the 9 EP studies were performed under general anesthesia, and one under conscious sedation. An accessory pathway was excluded in all patients by appropriate atrial and ventricular extrastimulus pacing techniques. Eight of the nine patients had dual AV nodal physiology, and one had single AV nodal echo beats. The slow AV nodal pathway was empirically ablated, by applying RF lesions in the right inferoseptal AV groove, achieving catheter tip temperature of 50 degrees C. The appearance of an accelerated junctional rhythm during RF application was deemed to denote a successful application site. AV conduction during RF application was confirmed by incremental atrial pacing. The catheter position, and its relation to the compact AV node was constantly monitored using the LocaLisa navigation system. The end-point was absence of dual AVN physiology, and/or AV nodal echo beats. RESULTS: Successful slow pathway ablation was achieved in all patients. One patient appeared to have two separate slow pathways with different locations and two AH-jumps, which were both successfully ablated. None of the patients had evidence of temporary or permanent AV block at follow-up (median duration 9 months, range 4 to 36 months); none has had recurrence of symptoms or documented tachyarrhythmia. CONCLUSIONS: In children with structurally normal hearts, a previously documented SVT, absence of an accessory pathway and noninducibility of SVT during EP study, empirical slow pathway ablation appears to be justified.

Adolescent↗

[10 years radiofrequency ablation of accessory conduction pathways].

Catheter ablation of the preexcitation syndrome is a curative treatment. Accessory pathways between structures of the specific conduction system or working myocardium are morphologic prerequisites for orthodromic or antidromic reentrant tachycardia of various frequency, duration, and rate. Detection of mechanisms of tachyarrhythmias and understanding the role of accessory pathways in tachycardia, mapping of accessory connections, function of nodal conduction system, and additional accessory pathways are necessary for successful catheter ablation. Anomalies of the tricuspid valve and coronary sinus and concomitant disease of the heart should be investigated prior to catheter ablation using echocardiography and contrast injection. Different variations of the preexcitation syndrome and the results of catheter ablation in 300 patients are demonstrated. Catheter ablation is indicated in refractory tachyarrhythmias on the basis of accessory pathways. The treatment is performed in a catheterization laboratory by two highly experienced cardiologists in the field of electrophysiology after training in 100 procedures. The investigators need experience in interventional treatment of coronary artery disease, in transseptal puncture, and in the management of complications (coronary and valvular problems, thromboemboly, and pericardial drainage). Catheterization needs careful protection of radiation. An ablation is possible at an atrial or ventricular insertion site of the accessory pathway or in between. Ablation is done during sinus rhythm, atrial stimulation, antidromic reentry, or atrial fibrillation or during ventricular pacing and orthodromic tachycardia. The procedure should end with bidirectional block of the accessory pathway in 90-95% of the patients. Complications occur in 2-4% of procedures. Recovery of accessory conduction is observed in 8%. Catheter ablation of the accessory pathway is the treatment of first choice in symptomatic patients with the pre-excitation syndrome. The procedure has limited risks and a high success rate.

Cardiac Pacing, Artificial↗

Alterations in Ca2+-dependent and cAMP-dependent signaling pathways affect neurogenesis and melanogenesis of quail neural crest cells in vitro.

Trunk neural crest cells primarily form neurons, nerve supportive cells of the peripheral nervous system and melanocytes. We are interested in signal transduction pathways that affect the production of peripheral neurons or melanocytes. Quail neural crest cell cultures were treated with a variety of drugs that affect components of protein kinase A- (PKA-), protein kinase C- (PKC-) and inositol-3-phosphate- (I3P-) dependent pathways. Forskolin, a drug that increases cAMP levels, augmented melanocyte populations and reduced neuronal populations in our cultures. H8 and H89, two drugs that inhibit PKA, reduced melanocyte populations well below control levels. Down regulation of PKC with a phorbol ester, PMA, or with calphostin C inhibited neurogenesis. PMA also enhanced melanogenesis. Increasing intracellular calcium levels (with A23187 or thapsigargin) resulted in cultures with few melanocytes but many neurons, compared to untreated controls. An antagonist of the I3P pathway, wortmannin, prevented the appearance of neurons but did not affect melanocyte populations. In summary, molecules that altered the PKA-dependent pathway affected melanogenesis. Manipulations of the I3P and/or PKC-dependent pathways influenced neurogenesis. Stimulation of one pathway often inhibited appearance of cells associated with the alternative pathway.

Animals↗

A PI3K pathway mediates hair cell survival and opposes gentamicin toxicity in neonatal rat organ of Corti.

Gentamicin is well known to promote hair cell death in inner ear, but it also appears to activate opposing pathways that promote hair cell survival. In combination with others, our previous work has indicated that a K-Ras/Rac/JNK pathway is important for hair cell death and an H-Ras/Raf/MEK/Erk pathway is involved in promoting hair cell survival (Battaglia et al., Neuroscience 122(4):1025-1035, 2003). However, these data also suggested that a Ras-independent survival pathway for activation of MEK might be stimulated by gentamicin. To investigate alternatives to the Ras/Raf/MEK/Erk pathway in promoting hair cell survival, cochlear explants were exposed to gentamicin combined with several inhibitors of alternative pathways (LY294002, calphostin C, SH-6, U73122). When exposed to gentamicin with the PI3K inhibitor LY294002 (10, 50 microM), the protein kinase C (PKC) inhibitor calphostin C (50, 100 nM) or the PKB/Akt inhibitor SH-6 (5, 10 microM), hair cell damage was significantly increased compared to gentamicin alone. By Western blotting, strong PKB/Akt activation was observed in the organ of Corti following exposure to 50 microM gentamicin for 6 h. In addition, PKC activation by 12-O-tetradecanoylphorbol-13-acetate protected outer hair cells from gentamicin induced cell death. In contrast, the phospholipase C-gamma (PLCgamma) inhibitor U73122 (2, 5 microM) did not affect hair cell damage when combined with gentamicin. Also, phosphorylation of PLCgamma was not increased in the organ of Corti following gentamicin treatment, as evaluated by Western blot. The results indicate that PI3K promotes hair cell survival via its downstream targets, PKC and PKB/Akt. This suggests that both Ras-dependent and Ras-independent survival pathways are involved during gentamicin exposure. In contrast, PLCgamma activation of PKC does not appear to play a role.

Animals↗

Assessment of the downstream portion of the mitochondrial pathway of caspase activation in patients with acute myeloid leukemia.

Most chemotherapeutic agents used in the treatment of acute myeloid leukemia (AML) induce apoptosis by triggering the mitochondrial pathway of caspase activation. To investigate the downstream portion of the mitochondrial pathway of caspase activation in patients with AML, cytosolic lysates were stimulated with cytochrome c and dATP and hydrolysis of Ac-DEVD-AFC by effector caspases was measured. Defects in the distal mitochondrial pathway were more common in samples from patients with AML that relapsed rapidly after induction chemotherapy compared to samples from treatment naïve patients. The incidence of blocked pathways did not differ based on response to induction chemotherapy, as even nonresponders generally had an intact pathway. When the distal mitochondrial pathway was blocked, defects were usually at the level of the effector caspases. Thus, functional defects in the distal portion of the mitochondrial pathway of caspase activation may help explain the nature of response and relapse after treatment.

Adenosine Triphosphate↗

Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: the role of death and survival signaling pathways.

The epidermis is confronted with multiple environmental and pathophysiological stresses. This study shows that TNFalpha, oxidative stress, hyperosmotic and heat shock induced both caspase-dependent and independent cell death in human HaCaT keratinocytes. The hormonal form of vitamin D, 1,25(OH)2D3, which is an autocrine hormone in the epidermis, protected the cells from all the examined stresses and pathways leading to cell death. We aimed to define the signaling pathways that determine the life-death balance of stressed keratinocytes and participate in their protection by 1,25(OH)2D3. As assessed by employing specific inhibitors, the survival pathways mediated by the EGF receptor, ERK, PI-3K or Src kinase, or basal transcriptional activity are important for unstressed cell survival. However, only the EGF receptor, PI-3K and the Src kinase pathways mediate the survival of stressed cells in a stimulus-specific manner. Inhibition of the p38 and/or the JNK death pathways reduced caspase activation induced by oxidative stress, hyperosmotic shock and TNFalpha. The protective effect of 1,25(OH)2D3 was not mediated by the examined survival pathways. 1,25(OH)2D3 inhibited the stress-induced activation of p38 and JNK. Since mimicking this effect by pharmacological inhibition resulted in the attenuation of caspase activation, we infer that these pathways are involved in keratinocyte protection by 1,25(OH)2D3.

Apoptosis↗

Comparative effects of adenosine triphosphate on accessory pathway and atrioventricular nodal conduction.

Adenosine triphosphate (ATP) has potent negative dromotropic effects on the atrioventricular (AV) node, but variable effects on accessory pathway conduction have been described. The effects of an intravenous bolus injection of 8 mg ATP on accessory pathway and AV nodal conduction were determined during electrophysiologic testing with controlled atrial and ventricular rates. AV conduction was monitored during atrial or ventricular pacing at a constant cycle length, 30 msec longer than the cycle length at which block occurred. During atrial pacing antegrade block after administration of ATP occurred in 1 of 30 (3.2%) patients with accessory pathway conduction and 12 of 13 (92%) patients with AV nodal conduction (p less than 0.001). During ventricular pacing only 5 of 26 (16%) patients had accessory pathways blocked, whereas 25 of 35 (71%) patients with AV nodal conduction had block (p less than 0.001). Thus, failure of ATP to produce ventriculoatrial block identified the presence of an accessory pathway with a sensitivity of 84%, specificity of 71%, and predictive value of 72%. There was no correlation between accessory pathway properties and the effects of ATP. The effects of ATP on the AV node were concordant with the effects of a combination of verapamil and propranolol in 21 of 23 patients, suggesting that this dose ATP is an equipotent AV nodal blocker with a short duration of action. Thus, although the effects of ATP on accessory pathways and the AV node differ, block in ventriculoatrial conduction after administration of ATP cannot be used as the sole criterion to distinguish the mechanism of conduction.

Adenosine Triphosphate↗

Catheter ablation of accessory atrioventricular pathways in 114 symptomatic patients with Wolff-Parkinson-White syndrome--a comparative study of direct-current and radiofrequency ablation.

To evaluate and compare the safety and efficacy of catheter-mediated direct-current and radiofrequency ablation in patients with Wolff-Parkinson-White syndrome, 114 patients with accessory pathway-mediated tachyarrhythmias underwent catheter ablation. Electrophysiologic parameters were similar in patients undergoing direct-current (group 1, 52 patients with 53 accessory pathways) and radiofrequency (group 2, 62 patients with 75 accessory pathways) ablation. Immediately after ablation, 50 of 53 accessory pathways (94%) were ablated successfully with direct current, but 2 of the 50 accessory pathways had early return of conduction and required a second ablation; 72 of 75 accessory pathways (96%) were ablated successfully with radiofrequency current. In the three accessory pathways in which radiofrequency ablation was unsuccessful, a later direct-current ablation was successful. During follow-up (group 1, 14 to 27 months; group 2, 8 to 13 months), none of the patients with successful ablation had a recurrence of tachycardia. Complications in direct-current ablation included transient hypotension (two patients), accidental atrioventricular block (one patient), and pulmonary air trapping (two patients); complications in radiofrequency ablation included cardiac tamponade (one patient) and suspicious aortic dissection (one patient). Myocardial injury and proarrhythmic effects were more severe in direct-current ablation. The length of the procedure and the radiation exposure time were significantly shorter in direct-current (3.5 +/- 0.2 hours, 30 +/- 4 minutes) than in radiofrequency (4.1 +/- 0.4 hours, 46 +/- 9 minutes) ablation. Findings in this study confirm the impression that radiofrequency ablation is associated with fewer complications than direct-current ablation and radiofrequency ablation with a large-tipped electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome.

Atrial Fibrillation↗

Two-dimensional echocardiographic assessment of caval and pulmonary venous pathways after the senning operation.

This study reports the 2-dimensional echocardiographic appearance of the caval and pulmonary venous pathways after the Senning procedure in 28 patients and establishes normal values for the caval and pulmonary venous pathway dimensions. Eighteen patients had no caval or pulmonary venous obstruction or tricuspid regurgitation at catheterization; 2 had isolated superior vena caval obstruction, 3 had isolated pulmonary venous obstruction, 4 patients had severe tricuspid regurgitation, and 1 had a large residual ventricular septal defect. The caval and pulmonary venous pathways were imaged in modified 4-chamber and transverse views, and the narrowest dimension of each pathway in each view was measured by 2 independent observers. Dimension measurements were then normalized to the cube root of body surface area. Caval and pulmonary venous pathway "dimension products" were obtained by multiplying the normalized dimension in the 4-chamber view by the normalized dimension in the transverse view. All patients with catheterization-proven caval or pulmonary venous obstruction or tricuspid regurgitation had caval or pulmonary venous pathway dimension products outside the normal range, defined by our measurements in the 18 patients with no caval or pulmonary venous obstruction or tricuspid regurgitation. Thus, 2-dimensional echocardiography can provide both quantitative and qualitative information about the caval and pulmonary venous pathways after the Senning procedure.

Child↗

Frequency, diagnosis and clinical characteristics of patients with multiple accessory atrioventricular pathways.

Multiple accessory atrioventricular (AV) pathways were documented in 52 of 388 patients (13%) who underwent detailed electrophysiologic evaluation. Multiple AV pathways were identified during intraoperative mapping or electrophysiologic study by different patterns of ventricular preexcitation during atrial fibrillation, flutter or atrial pacing with different delta-wave morphologic and ventricular activation patterns; different sites of atrial activation during right ventricular pacing or orthodromic reciprocating tachycardia; or preexcited reciprocating tachycardia using a second pathway as the retrograde limb of the tachycardia. A logistic model was used to determine which clinical, electrocardiographic and electrophysiologic variables were associated with multiple AV pathways. Right free-wall and posteroseptal accessory AV pathways were more common in patients with multiple AV pathways and were frequently associated. Multivariate logistic regression identified Ebstein's anomaly, and a history of preexcited reciprocating tachycardia as significant variables (p less than 0.0001). Pathway location was not subjected to statistical analysis because of confounding variables.

Adolescent↗

Effects of isoproterenol on accessory pathway conduction in intermittent or concealed Wolff-Parkinson-White syndrome.

The effects of isoproterenol on accessory pathway conduction were evaluated in 24 patients with intermittent and 60 patients with concealed pre-excitation, using atrial and ventricular incremental and extrastimulus testing techniques. The atrial paced cycle length that induced block in the accessory pathway could be compared in 11 of the 24 patients with intermittent preexcitation before and after isoproterenol; it decreased from 622 +/- 212 ms to 408 +/- 128 ms (mean +/- standard deviation) after isoproterenol (p less than 0.01). The anterograde effective refractory period of the accessory pathway could be compared in 5 patients before and after isoproterenol; it decreased from 460 +/- 131 to 310 +/- 48 ms after isoproterenol (p less than 0.01). None of the 60 patients with concealed preexcitation showed ventricular preexcitation with isoproterenol infusion. Eighty-one of the 84 patients had clinically documented supraventricular tachycardia, suggesting the accessory pathway was capable of retrograde conduction. Retrograde study was performed in all 84 patients; 83 had retrograde conduction and the other had no retrograde conduction before and after isoproterenol. The ventricular paced cycle length that induced block in the accessory pathway could be compared in 38 patients before and after isoproterenol; it decreased from 342 +/- 71 to 296 +/- 39 ms after isoproterenol (p less than 0.001). The retrograde effective refractory period of the accessory pathway could be compared in 56 patients; it decreased from 293 +/- 76 to 238 +/- 36 ms after isoproterenol (p less than 0.001). In conclusion, isoproterenol facilitates anterograde and retrograde accessory pathway conduction, but the facilitation of anterograde conduction occurs only in those capable of spontaneous conduction.

Adolescent↗

Reduction in medical care cost associated with radiofrequency catheter ablation of accessory pathways.

The cost of definitive therapy was compared in 25 patients who underwent radiofrequency catheter ablation of accessory pathways in 1990 and 25 patients who underwent surgical ablation of accessory pathways in 1989. In the radiofrequency group, 23 of 25 patients had a single accessory pathway and the remaining 2 patients each had 2 accessory pathways. In the surgical group, 20 patients had a single accessory pathway and 5 patients each had 2 accessory pathways. The success rate was 96% in each group. The mean duration of hospitalization was 3 +/- 1 days in the radiofrequency group and 9 +/- 4 days in the surgical group (p less than 0.0001). All the cost data are expressed in fiscal year 1990/1991 dollar values. The total cost of therapy in the radiofrequency group was $14,919 +/- $6,740 compared with $53,265 +/- $12,755 in the surgical group (p less than 0.0001). The cost of radiofrequency ablation consisted of a hospital charge of $7,753 +/- $3,472 and physician fees of $7,166 +/- $3,439. The hospital charge included charges for use of the electrophysiology laboratory, hospital stay, electrocardiograms, echocardiograms and blood studies. The cost of surgery consisted of a hospital charge of $37,708 +/- $10,179 and physician fees of $15,557 +/- $3,149. The hospital charge in the surgical group included the costs of a baseline electrophysiology study, in-hospital care and a follow-up office visit. In conclusion, radiofrequency catheter ablation of accessory pathways results in a dramatic reduction in the cost of definitive therapy in patients with the Wolff-Parkinson-White syndrome.

Adolescent↗