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PubMed1996

Temperature-controlled radiofrequency catheter ablation of manifest accessory pathways.

OBJECTIVES: The primary objectives of this study were to assess the feasibility of temperature-controlled radiofrequency catheter ablation of left and right sided manifest accessory pathways in patients with Wolff-Parkinson-White syndrome and to gain more insights into biophysical aspects of temperature-controlled catheter ablation in humans. BACKGROUND: The electrode-tissue interface temperature and other biophysical parameters are among important variables determining the efficacy and safety of radiofrequency ablation of accessory pathways. Experimental studies have shown that radiofrequency-induced tissue necrosis can be accurately predicted by monitoring of catheter tip temperature. METHODS: 38 consecutive patients (14 f, 24 m; aged 42 +/- 12 years) with anterograde conducting accessory pathways (left sided: n = 22; right sided: n = 16) underwent temperature-controlled radiofrequency ablation (HAT 200S, Dr Osypka, Germany). The electrode temperature was monitored via a thermistor embedded into a 4 mm catheter tip. Power output was adjusted automatically during energy delivery in a closed loop system (preselected temp.: 70.1 +/- 5.8 degrees C). RESULTS: Accessory pathway conduction was successfully abolished in all patients after the delivery of 2.3 +/- 2.1 radiofrequency pulses (range: 1-9, median: 2). Interruption of the accessory pathway as evidenced by loss of preexcitation occurred after 5.9 +/- 5.4 s. At the time of the interruption of the accessory pathway the catheter tip temperature measured 54.2 +/- 11.2 degrees C in patients with left and 44.9 +/- 5.0 degrees C in patients with right sided accessory pathways, respectively (P < 0.008). Higher temperature levels during left sided applications did not shorten the time it took for the effect to appear (left sided accessory pathway: 7.5 +/- 6.3 s, right sided accessory pathway: 3.7 +/- 2.9 s; ns). The catheter tip temperature was significantly higher during left compared to right sided applications after 5 (52.1 +/- 3.1 degrees C vs 47.2 +/- 4.3 degrees C) and 10 s (61.5 +/- 6.2 degrees C vs 52.7 +/- 4.2 degrees C) following initiation of the impulse (P < 0.005). Power output and delivered energy did not differ significantly at the time of accessory pathway abolition. Peak values of delivered power (45.1 +/- 10.9 W vs 41.3 +/- 10.6 W; P < 0.05) and total delivered energy (2452 +/- 1335 J vs 1392 +/- 762 J; P < 0.02) were significantly higher in the group of right sided pathways compared to left sided applications. The peak temperature measured 77.1 +/- 13 degrees C during effective and 69.9 +/- 14 degrees C during ineffective energy applications (P < 0.05). The time it took for the effect to appear was significantly longer in transiently effective pulses (10.4 +/- 7.2 s) compared to permanently effective applications (5.9 +/- 5.4 s; P < 0.02). Despite temperature control, an abrupt rise in impedance was observed in 10 of 89 (11%) energy applications. No procedure-related complications occurred. CONCLUSIONS: Temperature-controlled radiofrequency ablation of manifest accessory pathways is highly effective and safe. The temperature response is faster and significantly higher in left-sided energy applications compared to right-sided pulses. Peak temperature levels measured at the electrode tip are significantly higher during effective than ineffective pulses. Sudden rises in impedance are not completely prevented during temperature-controlled radiofrequency ablation of accessory pathway, although no procedure-related complications were noted in this patient cohort.

Adult↗
PubMed1990

Transthoracic defibrillation using sequential and simultaneous dual shock pathways: experimental studies.

Dual pathway sequential DC shocks reduce energy requirements for internal defibrillation. Our purpose was to determine if dual pathway shocks similarly reduce energy requirements or improve shock success in transthoracic (external) defibrillation. We studied 39 closed-chest anesthetized mongrel dogs. The dual pathways used were left chest to right chest and left chest to posterior. In eight dogs we also assessed dual shock pathways oriented orthogonally, left lower chest to right upper chest and left upper chest to right lower chest. Four different dual pathway groups were studied: group 1: simultaneous shocks, sinusoidal waveform; group 2: sequential shocks, sinusoidal waveform, 100-msec shock separation, orthogonal shock pathways; group 3: sequential shocks, sinusoidal waveform, 100 msec shock separation; and group 4: sequential shocks, rectangular waveform (sequential shocks: 2 pulses, 2.5 msec each, 0.1-msec separation; single shock: 1 pulse, 5 msec). Shocks were given at 50 (J) joules, 100 J and 150 J and curves of energy versus success compared for dual pathway shocks versus single shocks. We found that the highest mean success rates (96 +/- SD 9%) were achieved by simultaneous sinusoidal waveform dual pathway shocks at 100 J; this was identical to results achieved by the single pathway sinusoidal waveform comparison shocks at 100 J. Sequential dual pathway sinusoidal shocks separated by 100 msec achieved a mean success rate of 79 +/- 31% at 150 J; the comparison single pathway mean success rate was similar: 81 +/- 22% at 150 J. Thus, dual pathway sequential or simultaneous transthoracic shocks did not demonstrate clear superiority over single pathway shocks.

Animals↗
PubMed1983

Multiple pathways for isoleucine biosynthesis in the spirochete Leptospira.

Spirochetes of the genus Leptospira have previously been shown to use an unusual pathway to synthesize isoleucine. For reasons of convenience, we assume that only one unusual pathway is found in the genus, and we refer to it as the pyruvate pathway. We determined the distribution of this pyruvate pathway in representatives of the seven Leptospira DNA hybridization groups. Our method included labeling the representative strains with radioactive carbon dioxide and other radioactive precursors, fractionating the cells, and determining the specific activities (counts detected per nanomole) of the amino acids found in the protein fractions. On the basis of isoleucine biosynthesis, we found that the genus can be classified as follows: class I primarily, if not exclusively, uses the well-known threonine pathway; class II uses mostly the pyruvate pathway, with a minor amount of isoleucine being synthesized via the threonine pathway; and class III uses the pyruvate pathway exclusively. No relationship appears to exist between the degree of DNA hybridization and the classes of isoleucine biosynthesis. Although the precise intermediates on the pyruvate pathway are unknown, the origin of the carbon skeleton of isoleucine synthesized by this pathway is consistent with a borrowing of the leucine biosynthetic enzymes. However, we found that the pyruvate pathway is not controlled by leucine and that the two isoleucine pathways are independently regulated. Finding major and highly evolved multiple biosynthetic pathways of a specific amino acid within one genus is unique, and, conceivably, represents phylogenetic diversity within Leptospira.

Isoleucine↗
PubMed2005

Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles.

Contraction of esophageal (Eso) and lower esophageal sphincter (LES) circular muscle depends on distinct signal-transduction pathways. ACh-induced contraction of Eso muscle is linked to phosphatidylcholine metabolism, production of diacylglycerol and arachidonic acid (AA), and activation of the Ca(2+)-insensitive PKCepsilon. Although PKCepsilon does not require Ca(2+) for activation, either influx of extracellular Ca(2+) or release of Ca(2+) from stores is needed to activate the phospholipases responsible for hydrolysis of membrane phospholipids and production of second messengers, which activate PKCepsilon. In contrast, the LES uses two distinct intracellular pathways: 1) a PKC-dependent pathway activated by low doses of agonists or during maintenance of spontaneous tone, and 2) a Ca(2+)-calmodulin-myosin light chain kinase (MLCK)-dependent pathway activated in response to maximally effective doses of agonists during the initial phase of contraction. The Ca(2+) levels, released by agonist-induced activity of phospholipase C, determine which contractile pathway is activated in the LES. The Ca(2+)-calmodulin-MLCK-dependent contractile pathway has been well characterized in a variety of smooth muscles. The steps linking activation of PKC to myosin light chain (MLC20) phosphorylation and contraction, however, have not been clearly defined for LES, Eso, or other smooth muscles. In addition, in LES circular muscle, a low-molecular weight pancreatic-like phospholipase A2 (group I PLA2) causes production of AA, which is metabolized to prostaglandins and thromboxanes. These AA metabolites act on receptors linked to heterotrimeric G proteins to induce activation of phospholipases and production of second messengers to maintain contraction of LES circular muscle. We have examined the signal-transduction pathways activated by PGF(2alpha) and by thromboxane analogs during the initial contractile phase and found that these pathways are the same as those activated by other agonists. In response to low doses of agonists or during maintenance of tone, presumably due to low levels of calcium release, a PKC-dependent pathway is activated, whereas at high doses of PGF(2alpha) and thromboxane analogs, in the initial phase of contraction, calmodulin is activated, PKC activity is reduced, and contraction is mediated, in part, through a Ca(2+)-calmodulin-MLCK-dependent pathway. The PKC-dependent signaling pathways activated by PGF(2alpha) and by thromboxanes during sustained LES contraction, however, remain to be examined, but preliminary data indicate that a distinct PKC-dependent pathway may be activated during maintenance of tonic contraction, which is different from the one activated during the initial contractile response. The initial contractile response to low levels of agonists depends on activation of G(q). Sustained contraction in response to PGF(2alpha) may involve activation of the monomeric G protein RhoA, because the contraction is inhibited by the RhoA-kinase antagonist Y27632. This shift in signal-transduction pathways between initial and sustained contraction has been recently reported in intestinal smooth muscle.

Animals↗
PubMed2005

Signal transduction pathway profiling of individual tumor samples.

BACKGROUND: Signal transduction pathways convey information from the outside of the cell to transcription factors, which in turn regulate gene expression. Our objective is to analyze tumor gene expression data from microarrays in the context of such pathways. RESULTS: We use pathways compiled from the TRANSPATH/TRANSFAC databases and the literature, and three publicly available cancer microarray data sets. Variation in pathway activity, across the samples, is gauged by the degree of correlation between downstream targets of a pathway. Two correlation scores are applied; one considers all pairs of downstream targets, and the other considers only pairs without common transcription factors. Several pathways are found to be differentially active in the data sets using these scores. Moreover, we devise a score for pathway activity in individual samples, based on the average expression value of the downstream targets. Statistical significance is assigned to the scores using permutation of genes as null model. Hence, for individual samples, the status of a pathway is given as a sign, + or -, and a p-value. This approach defines a projection of high-dimensional gene expression data onto low-dimensional pathway activity scores. For each dataset and many pathways we find a much larger number of significant samples than expected by chance. Finally, we find that several sample-wise pathway activities are significantly associated with clinical classifications of the samples. CONCLUSION: This study shows that it is feasible to infer signal transduction pathway activity, in individual samples, from gene expression data. Furthermore, these pathway activities are biologically relevant in the three cancer data sets.

Breast Neoplasms↗
PubMed2005

Quantitative inference of dynamic regulatory pathways via microarray data.

BACKGROUND: The cellular signaling pathway (network) is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. RESULTS: In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network) to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network). Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. CONCLUSION: We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory pathway in Arabidopsis thaliana and metabolic shift pathway from fermentation to respiration in yeast Saccharomyces cerevisiae, are reconstructed using microarray data to evaluate the performance of our proposed method. In the circadian regulatory pathway, we identified mainly the interactions between the biological clock and the photoperiodic genes consistent with the known regulatory mechanisms. We also discovered the now less-known regulations between crytochrome and phytochrome. In the metabolic shift pathway, the casual relationship of enzymatic genes could be detected properly.

Algorithms↗
PubMed2006

cPath: open source software for collecting, storing, and querying biological pathways.

BACKGROUND: Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. RESULTS: We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third-party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. CONCLUSION: cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling.

Computational Biology↗
PubMed2004

Cooperative function of Chk1 and p38 pathways in activating G2 arrest following exposure to temozolomide.

OBJECT: The Chk1 and p38 mitogen-activated protein kinase (MAPK) pathways play key roles in the G2 arrest caused by exposing glioma cells to temozolomide (TMZ). Although inhibition of either pathway sensitizes glioma cells to TMZ-induced cytotoxicity, the relative contributions of these pathways to TMZ-induced G2 arrest and to TMZ resistance conferred by G2 arrest have not been defined. METHODS: The authors pharmacologically inhibited the Chk1 and/or p38 pathways in U87MG human glioma cells prior to and/or after exposure to TMZ; thereafter, effects on the TMZ-induced G2 arrest pathway and toxicity were monitored. The p38 inhibitor SB203580 or the Chk1 inhibitor UCN-01 or their combination blocked TMZ-mediated inactivation of cdc25C and cdc2, suggesting that p38 and Chk1 pathways work cooperatively and are both necessary to inactivate cdc25C and cdc2. Consistent with this idea, the inhibition of both Chk1 and p38 pathways did not lead to greater bypass of TMZ-induced G2 arrest or greater cytotoxicity than inhibition of either pathway alone. Inhibition of p38 did not alter TMZ-induced Chk1 activation/phosphorylation and vice versa, suggesting that p38 and Chk1 do not cooperatively bring about G2 arrest by reciprocal activation/phosphorylation. The two pathways, however, are not functionally identical; the Chk1 pathway was required for both the initiation and maintenance of TMZ-induced G2 arrest, whereas the p38 pathway played a role only in the initiation. CONCLUSIONS: The Chk1 and p38 pathways cooperate to bring about TMZ-induced G2 arrest, and the inhibition of either pathway alone is sufficient to sensitize U87MG glioma cells to TMZ-induced cytotoxicity.

Antineoplastic Agents, Alkylating↗
PubMed2000

[Radiofrequency catheter ablation of left-sided atrioventricular accessory pathways. Immediate and long-term results using the trans-aortic approach].

UNLABELLED: Catheter mapping and ablation of left accessory pathways may be difficult if the pathway fibre orientation is oblique across the mitral annulus. This is particularly true in case of concealed accessory pathway that conducts only in ventriculoatrial direction. The purpose of the study was to compare catheter ablation safety, efficacy, procedure and fluoroscopy times and number of radiofrequency energy deliveries for manifest and concealed left accessory pathways using retrograde transaortic approach. 56 patients (26 females) aged 41.6 +/- 15.1 years underwent 59 ablation procedures for 59 left accessory pathways. 25 (44.6%) patients with 27 concealed accessory pathways and additional 2 patients with a manifest pathway mappable only during retrograde conduction formed group I and were compared to 29 patients with a manifest accessory pathway mappable during ventricular preexcitation (group II). Ablation was acutely successful in all patients. Reablation was necessary for the pathway recurrence in 2 patients and for a different pathway in 1 patient. Deep femoral venous thrombosis complicated ablation in 1 patient. During the 14.9 +/- 8.2 (3-30) month follow-up period all the patients remain free of a pathway related tachyarrhythmia. Both the groups (I vs II) did not differ in procedure (180 +/- 76.7 vs. 187 +/- 75.8; p = 0.36) and fluoroscopy (25.3 +/- 18.6 vs. 33.5 +/- 24.7; p = 0.08) times (min) and number of radiofrequency energy deliveries (10.0 +/- 9.2 vs. 10.2 +/- 9.8; p = 0.46). CONCLUSION: Transaortic approach to the left concealed accessory pathways is safe and effective in virtually 100% of patients and, compared to manifest pathways, does not prolong procedure and fluoroscopy times nor the number of radiofrequency energy deliveries.

Adolescent↗
PubMed1992

Mechanism of bradycardia-dependent appearance of manifest extrasystoles in concealed bigeminy. A theoretical model derived from the concepts of longitudinal dissociation and multilevel block in the reentrant pathway of extrasystoles.

A case of bradycardia-dependent appearance of manifest extrasystoles in concealed bigeminy is presented. To explain the mechanism of such bradycardia-dependent appearance, a theoretical model is derived from the concepts of "longitudinal dissociation" and "multilevel block" in the reentrant pathway of extrasystoles. In the theoretical model, functional longitudinal dissociation divides the reentrant pathway into dual pathways F and S. When manifest extrasystoles are not found for a long time, alternate sinus impulses pass through both pathways F and S, but become concealed extrasystoles because of insufficient conduction delay in the pathways. The other alternate sinus impulses are blocked in the pathways; in pathway F, the impulses are blocked at the entrance, while in pathway S, the impulses are blocked at a more distal level. When sinus cycles gradually lengthen, one of such alternate sinus impulses passes through the entrance of pathway F and, traveling very slowly, is blocked at a more distal level. The next sinus impulse is blocked at the entrance of pathway F; namely, 3:2 Wenckebach block occurs at the entrance of pathway F. Thus this sinus impulse enters only pathway S and passes through pathway S with enough conduction delay to become a manifest reentrant extrasystole.

Bradycardia↗
PubMed1997

One-year experience with an inpatient asthma clinical pathway.

OBJECTIVE: To study the effects of an inpatient asthma clinical pathway on the processes and outcomes for children who were admitted to a hospital for the treatment of asthma. DESIGN: Before-and-after study. SETTING: A private nonprofit academic children's hospital in Seattle, Wash. PATIENTS AND METHODS: Three hundred forty-two admissions of 297 patients in the first year of the asthma clinical pathway were compared with 353 admissions of 292 similar patients in the previous year. Patients who required intensive care, were younger than 2 years, or had a major chronic disease were excluded. INTERVENTION: Asthma was chosen for the development of a clinical pathway because of its large number of admissions, involvement of multiple health care providers (nurses, physicians, and respiratory therapists), predictable hospital course, and variable lengths of hospital stay. The pathway was a consensus-based guideline for patient management that was intended to be adapted to the care of an individual patient. Prior to the implementation of the clinical pathway, nurses, attending physicians, house staff, and respiratory therapists were trained in its use. The main hospital chart of each patient who was admitted to the pathway had a flowchart that outlined day-to-day guidelines for monitoring and care. Nursing staff were responsible for documenting when a patient's care varied from the pathway, and these variances were entered into a computer database. OUTCOME MEASURES: Use of peak flowmeters, steroids, laboratory studies, radiological studies, and respiratory therapy was assessed by analyzing the patients' electronic billing records. For patients enrolled in the pathway, additional data on process of care were obtained by analyzing the variance database. For both groups, the total charges, length of stay, and rate of readmission to the hospital were measured by use of the billing records. RESULTS: There were no significant differences in the use of steroids or peak flowmeters, average lengths of stay, or total charges between the 2 groups. However, patients in the "pathway group" had significantly lower average charges for laboratory ($26 vs $39; P < .05) and radiology ($32 vs $55; P < .001) services. Variances from the pathway guidelines were most often related to the patients' responses to therapy. CONCLUSIONS: The asthma clinical pathway had no effect on clinical outcomes and small effects on the use of resources. Further development, including physician and nurse training, computer and administrative support, and clinical severity scales, are needed to develop the potential utility of the clinical pathway as a research and quality assurance tool.

Adolescent↗
PubMed1986

Optic fibers follow aberrant pathways from rotated eyes in Xenopus laevis.

The rotated eye paradigm has been a major experimental test of the neuronal specificity model for the development of ordered retinotectal connections in amphibians. In most studies, however, no optic fiber pathways were traced from rotated eyes and correlated with visuotectal projections. As an initial approach to this question, optic fibers from eyes rotated at different embryonic stages were traced with 3H-proline autoradiography. Three experimental series were prepared: in situ eye rotations, isochronic transplants of eyes rotated between embryos at the same stage, and heterochronic transplants of eyes rotated between embryos at different stages. Single or multiple optic fiber pathways developing from rotated eyes are identified by their sites of entry and trajectory in the brain. These include a normal chiasmatic (CH) pathway, and three aberrant pathways, identified as trigeminal (TR), diencephalic (DI), and oculomotor (OC). The latter three enter the brain ipsilaterally, some crossing contralaterally via commissural pathways. Depending on stage and type of operation, TR pathways develop in 50-100% of the animals, while CH pathways are more common after rotation at stage 21/22. The surgical procedure affects the initial trajectory of fibers from the retina, perturbs guidance cues in the surrounding orbit, and determines the patterns of optic pathways that develop. In most cases, optic fibers follow motor (oculomotor) or sensory (trigeminal) nerves, usually the first fibers encountered near the orbit by axonal pioneers exiting the retina. Evidently, optic fibers exhibit no pathway selectivity; any axon serves as a guidance cue. Tecta are innervated in about 50% of the cases, usually by fibers following abnormal trajectories from CH and OC pathways. The results suggest that the development of ordered visuotectal projections from rotated eyes is a complex process that may be independent of the trajectory of fiber arrival. Unless pathways and visuotectal maps are directly compared in each animal, however, the question remains open because we still do not know which anomalous pathways, if any, correlate with ordered projections.

Animals↗
PubMed1987

Mechanism and quantitative contribution of the pentose pathway to the glucose metabolism of Morris hepatoma 5123C.

An investigation of the mechanism and quantitative contribution of the pentose phosphate pathway in the glucose metabolism of Morris Hepatoma 5123C is reported. Morris Hepatoma 5123C has an active non-oxidative segment of pentose pathway as judged by its ability to convert ribose 5-P to hexose 6-P in a standard assay. Based on compliance with qualitative and quantitative criteria, the cells exhibit the L-type pentose pathway reaction sequence rather than the F-type pathway. This compliance included the formation of intermediates characteristic of the L-type pathway, namely arabinose 5-P, octulose mono- and bisphosphates and sedoheptulose 1,7-bisphosphate, during the dissimilation of ribose 5-P to hexose 6-P. The intermediary role of arabinose 5-P was suggested by the incorporation of its carbon into various intermediates and products of the pentose pathway. Intermediary roles for ido octulose mono- and bisphosphates were supported by their participation in the reaction catalyzed by the phosphotransferase enzyme of the L-type pentose pathway. Presence of L-type PP reactions was further affirmed by 14C-prediction labelling experiments using [5-14C]- and [2-14C]glucose as specifically labelled substrates. Using two methods of measurement, the F-type pentose cycle made a negligibly small contribution to glucose metabolism, while the measured value of the L-type pentose pathway accounted for 30% (approx.) of the total glucose metabolism of these cells, a value consistent with the high activity of the enzymes of the L-type pentose pathway in Morris Hepatoma 5123C cells and the very high activity of the non-oxidative segment of the pathway in vitro. The findings validate the proposal that the L-type pentose pathway reactions constitute the non-oxidative segment of the pathway in Morris Hepatoma 5123C cells. Reasons involving pyruvate recycling reactions show why there is low incorporation of 14C-isotope in C-1 of glucose 6-P, when [4,5,6-14C]glucose and [6-14C]glucose are L-type PP test substrates in intact cells.

Animals↗
PubMed1988

Surgical division of Wolff-Parkinson-White pathways utilizing the closed-heart technique: a 2-year experience in 47 patients.

Kent bundle interruption for ventricular preexcitation has been successfully accomplished utilizing several different surgical techniques. The external closed-heart technique of Guiraudon combining surgical dissection and cryoablation has been used to interrupt 52 accessory pathways in 47 consecutive patients since May, 1985. The 35 male and 12 female patients ranged in age from 10 to 67 years (mean, 30 years). There were 25 left free wall, 13 right free wall, 13 posterior septal, and 1 anterior septal accessory pathways. Preoperative and intraoperative electrophysiological studies were performed in all patients to induce the arrhythmia and localize all accessory pathways. The operation consisted of dissection of the atrioventricular fat pad. Following this, the delta wave and retrograde accessory pathway conduction disappeared, thereby indicating successful pathway ablation. In 4 patients with right-sided accessory pathways, interruption of the pathway required cryoablation. Cryolesions (made with cryoprobe at -60 degrees C for two minutes) were created in the region of the accessory pathway insertion. All accessory pathways were successfully ablated without any deaths or heart block. Concomitant surgical procedures were performed in 4 patients. Two patients required a second operation the next day for an accessory pathway not found at the initial operation. Three patients had postpericardiotomy syndrome, and 4 had recurrent atrial fibrillation requiring therapy. The remaining patients have had no arrhythmia recurrence and have remained drug free after a follow-up of 1 month to 22 months (mean, 12.5 months). We conclude that the closed-heart technique of accessory pathway ablation is safe and reproducible, obviates the necessity for aortic cross-clamping and cardioplegic arrest, and allows instantaneous monitoring of conduction over the pathway.

Adolescent↗
PubMed2005

[Evaluation of a clinical pathway for laparoscopic cholecystectomy].

INTRODUCTION: Clinical pathways are standardized plans for the integral care of specific processes. In March 2002, a clinical pathway for laparoscopic cholecystectomy was introduced in our service. The aim of the present study was to evaluate this pathway 1 year after its implementation. METHODOLOGY: All patients included in the clinical pathway since its introduction were studied. Evaluation criteria included compliance, indicators of the effectiveness of clinical care, economic impact and indicators of satisfaction based on a survey. The results were compared with those in a series of patients who underwent surgery in the year before the introduction of the clinical pathway. Our hospital uses analytical accounting and the mean cost per process before and after the introduction of the clinical pathway was analyzed. RESULTS: A series of 160 consecutive patients who underwent surgery during the year prior to the creation of the clinical pathway and who fulfilled the accepted inclusion criteria was evaluated. The mean length of hospital stay was 3.27 days. The mean cost per process before the introduction of the pathway was 2149 (+/- 768) euros. During the first year after the introduction of the pathway, 140 patients were included with an inclusion rate of 100%. The mean length of hospital stay in patients included in the clinical pathway was 2.2 days. The degree of compliance with length of hospital stay was 66.7%. The most frequent causes of breach were staff-related, followed by patient-related (oral intolerance, pain, etc.). The mean cost in patients included in the clinical pathway was 1845 (+/- 618) euros. CONCLUSIONS: Laparoscopic cholecystectomy is a suitable process with which to initiate systematization of clinical pathways. The results show that length of hospital stay has been significantly reduced without increasing morbidity. Patient satisfaction has been high.

Cholecystectomy, Laparoscopic↗
PubMed1998

The role of nitric oxide in development of the patch-cluster system and retinocollicular pathways in the rodent superior colliculus.

Nitric oxide (NO) has been implicated as a retrograde signal in the process of refining axonal pathways during brain development. To determine some of the factors involved in this process, we have used two model pathway systems in the rat and mouse superior colliculus (SC). The first, the patch-cluster system, consists of clusters of neurons in the intermediate gray layer (igl) which transiently express NO during development and which receive input from a cholinergic pathway from the parabrachial brainstem as well as from other pathways containing different transmitters. The second system, the retinocollicular pathway, consists of glutamatergic fibers that project to the superficial gray layer. We have used both nitric oxide synthase inhibition (nw-nitro-L-arginine, NoArg) and single (nNOS) and double (nNOS and eNOS) gene knockout mice to examine the effect that reduction in NOS has upon the development of these two systems. The onset of NOS expression in rat, as revealed by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeling, occurred in igl cells as early as postnatal day P5, with clusters being well-established by P14. Cholinergic fibers were first visible at P10 and formed obvious patches and tiers by P14. Intraperitoneal injections of NoArg from P1-P22 had no effect upon the development of these cholinergic patches. The pathway also developed normally in both single and double-knockout mice. In contrast, the ipsilateral retinocollicular pathway was altered in the double, but not in the single knockout mouse. This pathway is exuberant during the first week of life, being distributed across much of the mediolateral axis of the rostral SC. By P8-P15, this pathway has retracted to the most mediorostral SC. This refinement was delayed substantially in the double NOS gene knockout mouse. Ipsilateral fibers were found within 3-5 separate medio-lateral patches within the rostral 600 microns of SC at P15, and patches of abnormal size and extent were also seen at P18. We conclude from these results that NO plays a role in pathway development in the rodent SC, but only in glutamatergic pathways and only when both endothelial and neuronal forms of NOS have been deleted. The mechanism of this effect must involve pathway elimination in situations where there is non-correlated electrical activity. It is likely that NO promotes fiber retraction rather than fiber stabilization in these developing nerve fibers.

Acetylcholine↗
PubMed2000

Merging clinical pathway programs as part of overall health system mergers: a ten-step guide. Spectrum Health.

BACKGROUND: Mergers, acquisitions, and reorganizations can be stressful and accompanied by ambivalence, confusion, and uncertainty. Providing clear and simple steps for merging clinical pathways may help organizations move through the transition process more smoothly. The ten steps according to which Spectrum Health merged its pathway program-conduct an inventory of previous efforts, plan for the ideal program, bring staff together early in the merger process, decide on a common format, standardize the development and revision process, standardize a reporting tool, create a clinical pathway manual, implement an educational plan, present the program to key customers, and appoint an advisory group-need not be done sequentially. The ten-step pathway merger program uses pathways as a means to improve the quality of the care provided, with a focus on multidisciplinary clinical pathway teamwork. Before the merger, the two hospital systems' pathway programs used different approaches to operations and pathway format. When the announcement to merge came in September 1997, steps to merge the clinical pathway programs began. DISCUSSION: More than two years into the merger, Spectrum Health continues to struggle with the evolution of the health system. Clinical pathways represent just one of the significant and extensive issues related to organizational mergers; organizational values, finances, vision, mission, customer relations, strategic priorities, and people issues are a few of the others. Focusing on merging programs such as clinical pathway programs can help put one large piece of the merger puzzle in place and reduce some of the ambiguity associated with all mergers. Executive support is critical to the success of the clinical pathway program.

Critical Pathways↗
PubMed2000

Care pathways: an evaluation of their effectiveness.

This paper reports on a quasi-experimental case study of two care pathways--a midwifery-led maternity pathway and a breast disease pathway developed within one British National Health Service Trust. Of the aspects evaluated, those reported here are: a comparison of clinical care delivered before (the control group) and after the introduction of the two pathways; a comparison of patient satisfaction levels before (the control group) and after the introduction of the two pathways; and views of staff involved in the development and operation of the two pathways. The results are mixed. In the breast disease pathway five of 12 clinical indicators showed change, but only two of these showed statistically significant changes; three were considered of clinical significance but could not be tested statistically. In the maternity pathway, after allowing for the effect of gravid status, five of 10 indicators showed changes between the pre-pathway and pathway users and of these four showed statistically significant changes. Patient satisfaction levels showed little overall change--only 15% of the questions for breast disease and 9% for maternity showed any statistically significant change. However, both surveys indicated precise areas where a change resulting from the introduction of the pathway could be linked to an increase in satisfaction. The clinical staff interviewed highlighted many positive features of the tool (26/40 comments). The most frequently cited favourable comment was its ability to make staff focus on the clinical care they were providing and how this could be improved. It also highlighted some areas for concern, in particular the introduction of pathway documentation.

Attitude of Health Personnel↗