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PubMed2003

Multiple accessory pathways in pediatric patients with Wolff-Parkinson-White syndrome.

The characteristics of multiple accessory pathways in children have not been previously studied. Records were reviewed of 317 consecutive pediatric patients with Wolff-Parkinson-White syndrome who underwent electrophysiologic study and radiofrequency catheter ablation at our institution. Twenty-eight patients (9%) had multiple pathways (a total of 64 pathways: 21 patients had 2, 6 had 3, and 1 patient had 4 pathways). The locations were left free wall (22 pathways), right free wall (19 pathways), posteroseptal (17 pathways), and anteromidseptal (6 pathways). Of these 64 pathways, 55 were ablated successfully without complications, 5 failed ablation, and 4 fasciculoventricular fibers did not require treatment. Three patients had a newly found pathway at the repeat session. Three patients had atrioventricular nodal reentrant tachycardia and the slow pathway area was modified. One patient had failed initial ablation and had a successful ablation using a 3-dimensional electroanatomic mapping system. Compared with patients with a single pathway, those with multiple pathways exhibited a higher incidence of antidromic tachycardia, a shorter anterograde accessory pathway effective refractory period (<250 ms), a longer fluoroscopic time (65 +/- 43 vs 39 +/- 46 minutes, p <0.05), and a larger number of unsuccessful attempts (9 +/- 16 vs 5 +/- 8, p <0.05). Success rate (92% vs 93%) and recurrence rate (1.7% vs 2.1%) were similar in both groups. This study demonstrates that multiple pathways are not rare in pediatric patients and that multiple pathways contrast with a single pathway in a variety of conduction properties.

Adolescent↗
PubMed1989

Differential effects of leupeptin, monensin and colchicine on ligand degradation mediated by the two asialoglycoprotein receptor pathways in isolated rat hepatocytes.

We have shown that degradation of asialo-orosomucoid (ASOR) in isolated rat hepatocytes occurs by two different intracellular pathways [Clarke, Oka & Weigel (1987) J. Biol. Chem. 262, 17384-17392] mediated by two subpopulations of cell surface galactosyl (Gal) receptors, designated State 1 or State 2 receptors. In the present study, several inhibitors were tested for their effects on ligand degradation by the State 1 or State 2 pathway. Leupeptin, monensin and chloroquine completely inhibited degradation of 125I-labelled ASOR in both pathways. Dose-response studies showed, however, that the State 2 pathway was more sensitive to leupeptin or monensin than the State 1 pathway. No differences were observed with chloroquine. For example, the onset of inhibition in the State 2 and State 1 pathways occurred at about 0.05 and 0.3 microM-leupeptin respectively, a 6-fold difference. At 3.5 microM-monensin, 125I-ASOR degradation in the State 2 pathway was completely blocked, whereas degradation in the State 1 pathway was essentially unaffected. Colchicine was observed to give the largest differential sensitivity between the two pathways. The State 2 degradation pathway was about 30-fold more sensitive to colchicine than the State 1 pathway. Lumicolchicine had no affect. The onset of inhibition of the rate of 125I-ASOR degradation in the State 2 and State 1 pathways occurred at approximately 0.1 and 3.0 microM-colchicine respectively. At very high concentrations (greater than 0.1 mM), the State 1 pathway could be completely inhibited. We conclude that intracellular 125I-ASOR processing or delivery to degradative compartments in both the State 1 and State 2 Gal receptor pathways requires low pH. Ligand delivery to the degradative compartment does not require microtubules in the State 1 pathway, consistent with the very rapid onset of degradation in this pathway. The State 2 degradation pathway does require microtubules.

Animals↗
PubMed1998

Impact of a clinical pathway for radical retropubic prostatectomy.

OBJECTIVES: Cost containment has become an important issue in medical practice. With the implementation of collaborative care programs and critical pathways, substantial reduction in overall costs can be achieved while maintaining the quality of care and patient satisfaction. METHODS: Our series consists of 856 consecutive patients treated with radical retropubic prostatectomy by 24 surgeons in a single hospital between January 1, 1994, and January 31, 1997. A clinical pathway for radical retropubic prostatectomy was implemented July 1, 1994. The patients were subdivided into three groups: (1) baseline: patients who underwent surgery in the 6 months immediately before the pathway onset (n = 113); (2) nonpathway: 75 patients treated off the clinical pathway; and (3) pathway: 668 men placed on the clinical pathway. We compare average length of stay and average hospital charges among the three groups. We also compare average length of stay among physician volume groups: high volume physicians performed at least 12 operations per year; low volume physicians performed less than 12 operations per year. Charges were further broken down by department. Patient satisfaction was recorded by an outside source after discharge. Postoperative complications were assessed in the clinical pathway and nonpathway groups. RESULTS: Average hospital charges and average length of stay were $12,926 and 5.8 days for baseline patients, $11,795 and 5.0 days for nonpathway patients, and $10,042 and 4.0 days for pathway patients, respectively. Implementation of the clinical pathway was associated with lower charges and length of stay in the pathway group as well as the nonpathway group, with larger reductions in pathway patients. With continuous reassessment and modification of the clinical pathway, both average hospital charges and average length of stay have progressively decreased from $10,540 and 4.9 days in 1994 to $8766 and 2.7 days in January 1997. Charges were uniformly reduced in radiology, laboratory, pharmacy, operating room, anesthesia, and nursing or routine care. Patient satisfaction was similar in the pathway group and the nonpathway group. Incidence of postoperative complications did not differ significantly between the pathway and nonpathway groups. Length of stay and hospital charges were significantly lower for high than low volume surgeons, irrespective of the declines observed over time (P = 0.0001 and 0.0001, respectively). CONCLUSIONS: Average hospital charges and average length of stay for all surgeons were lowered significantly with the implementation of a clinical pathway and continue to decrease with continuous reassessment. The pathway was not associated with any increase in postoperative complications or patient dissatisfaction. Surgeons who operate frequently have lower average lengths of stay and hospital charges than those who operate infrequently.

Adult↗
PubMed1999

Calcium-independent haemolysis via the lectin pathway of complement activation in the guinea-pig and other species*.

We previously reported that complement-dependent haemolysis of sheep erythrocytes (E) coated with mannan (M) and sensitized with human mannan-binding lectin (MBL) via the lectin pathway in man occurs in Mg-EGTA and requires alternative pathway amplification. Calcium was required for MBL binding to E-M, but once the E-M-MBL intermediate was formed, MBL was retained and haemolysis occurred in the absence of calcium. Comparable or greater lectin pathway haemolysis in the absence of calcium was observed upon incubation of E-M-MBL in guinea-pig, rat, dog and pig sera, and was further investigated in the guinea-pig, in which titres were much higher ( approximately 14-fold) than in man, and in contrast to humans, greater than classical pathway haemolytic activity. As in human serum, no lysis was observed in C4- or C2-deficient guinea-pig serum until purified C4 or C2, respectively, were restored. However, lectin pathway haemolytic activity in the guinea-pig did not require the alternative pathway. Removal (>98%) of factor D activity by three sequential passages through Sephadex G-75, resulting in serum which retained a normal classical pathway but no alternative pathway haemolytic activity, did not reduce the ability of guinea-pig serum to mediate haemolysis via the lectin pathway. Further, the C3-convertase formed via the lectin pathway (E-M-MBL-C4,2) lysed in C2-deficient guinea-pig but not human serum chelated with EDTA, a condition which precludes alternative pathway amplification. Thus, lectin pathway haemolysis occurs efficiently in guinea-pig serum, in the absence of calcium and without requirement for alternative pathway amplification. The guinea-pig provides a model for studying the assembly and haemolytic function of a lectin pathway which contrasts with the lectin pathway of man, and allows for comparisons that may help clarify the role of this pathway in complement biology.

Animals↗
PubMed2003

Use of critical pathways to improve efficiency: a cautionary tale.

BACKGROUND: Critical pathways are healthcare management plans that specify patient goals and the sequence and timing of actions necessary to achieve these goals with optimal efficiency. More than 80% of hospitals in the United States use critical pathways for at least some of their patients. Unfortunately, critical pathway effectiveness in improving clinical efficiency is unclear. OBJECTIVES: To assess whether critical pathways have been successful in reducing patient length of stay (LOS) and resource utilization in our tertiary-care academic medical center. STUDY DESIGN: A before-and-after observational study using multivariate linear regression analyses. METHODS: We identified all critical pathways initiated in our medical center between 1993 and 1996 in which at least 50 adult patients would be evaluated in the year preceding and succeeding pathway implementation; 13 pathways satisfied these inclusion criteria. Using a before-and-after design, multivariate linear regression was used to evaluate each pathway's effect on average monthly LOS and resource utilization after adjusting for case mix and secular trends. RESULTS: Three of the 13 pathways were associated with a statistically significant immediate decrease in inpatient LOS: acute myocardial infarction (20.7% decrease; P = .001), cesarean section (14.6% decrease; P = .03), and kidney transplantation (24.5% decrease; P = .003). Only 1 pathway, percutaneous transluminal coronary angioplasty (PTCA), produced a statistically significant decrease in LOS slope (a decrease of 5.2% per month; P = .001). Two pathways were accompanied by a statistically significant immediate reduction in ancillary resource utilization: kidney transplantation (26.4% decrease; P = .001) and community-acquired pneumonia (21.8% decrease; P = .002). Only the PTCA pathway produced a statistically significant decrease in resource utilization slope during the 12-month follow-up period (a decrease of 8.4% per month; P < .001). CONCLUSIONS: Although some pathways did reduce LOS or resource utilization or both, most pathways reduced neither. Because substantial resources must be expended on pathway development, implementation, and maintenance, future efforts should be placed on further evaluating the effectiveness of critical pathways and understanding the reasons behind their success or failure before additional resources are consumed for this management strategy.

Critical Pathways↗
PubMed1993

Selective radiofrequency catheter ablation of fast and slow pathways in 100 patients with atrioventricular nodal reentrant tachycardia.

One hundred patients received selective radiofrequency ablation of retrograde fast pathway (32 patients, group I) or slow pathway (68 patients, group II) to treat drug-refractory atrioventricular nodal reentrant tachycardia. In group I, a mean of 6 +/- 3 radiofrequency pulses eliminated the retrograde fast pathway. Thirty patients were free of symptoms and were not receiving antiarrhythmic drugs; two patients had accidental atrioventricular block. One patient had recurrent tachycardia and received a repeated ablation (slow pathway ablation). In group II, a mean of 9 +/- 4 radiofrequency pulses eliminated the slow pathway in 68 patients. All patients were free of symptoms and were not receiving antiarrhythmic drugs. One patient had recurrent tachycardia and received a repeated ablation. Serial follow-up electrophysiologic studies (immediate [20 to 30 minutes], early [5 to 7 days], and late [3 to 6 months]) showed that selective ablation of retrograde fast pathway was associated with nonspecific injury on the antegrade fast pathway (increase of AH interval) without effects on the slow pathway. Selective ablation of slow pathway was associated with nonspecific injury on the retrograde fast pathway in 15 patients (22%), but the antegrade fast pathway conduction parameters did not change significantly. Thus retrograde and antegrade fast pathway may be anatomically similar or have different sensitivities to radiofrequency energy, and slow pathway may be anatomically distinct from fast pathway. We conclude that (1) selective radiofrequency ablation of retrograde fast or slow pathway could cure atrioventricular nodal reentrant tachycardia with a high success rate (98%) and a low recurrence rate (2%) during a follow-up period of 6 to 18 months, but fast pathway ablation was associated with accidental atrioventricular block (5%), and (2) serial follow-up electrophysiologic studies elucidated the possible mechanisms of cure in atrioventricular nodal reentrant tachycardia.

Adolescent↗
PubMed2005

Pathway recognition and augmentation by computational analysis of microarray expression data.

MOTIVATION: We present a system, QPACA (Quantitative Pathway Analysis in Cancer) for analysis of biological data in the context of pathways. QPACA supports data visualization and both fine- and coarse-grained specifications, but, more importantly, addresses the problems of pathway recognition and pathway augmentation. RESULTS: Given a set of genes hypothesized to be part of a pathway or a coordinated process, QPACA is able to reliably distinguish true pathways from non-pathways using microarray expression data. Relying on the observation that only some of the experiments within a dataset are relevant to a specific biochemical pathway, QPACA automates selection of this subset using an optimization procedure. We present data on all human and yeast pathways found in the KEGG pathway database. In 117 out of 191 cases (61%), QPACA was able to correctly identify these positive cases as bona fide pathways with p-values measured using rigorous permutation analysis. Success in recognizing pathways was dependent on pathway size, with the largest quartile of pathways yielding 83% success. In cross-validation tests of pathway membership prediction, QPACA was able to yield enrichments for predicted pathway genes over random genes at rates of 2-fold or better the majority of the time, with rates of 10-fold or better 10-20% of the time. AVAILABILITY: The software is available for academic research use free of charge by email request. SUPPLEMENTARY INFORMATION: Data used in the paper may be downloaded from http://www.jainlab.org/downloads.html

Algorithms↗
PubMed1998

Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways.

There are several pathways for the incorporation of sugars into glycosphingolipids (GSL). Sugars can be added to ceramide that contains sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to ceramide synthesized from sphingoid bases produced by hydrolysis of sphingolipids (pathway 2), and into GSL recycling from the endosomal pathway through the Golgi (pathway 3). We reported previously the surprising observation that SW13 cells, a human adrenal carcinoma cell line, synthesize most of their GSL in pathway 2. We now present data on the synthesis of GSL in four additional cell lines. Approximately 90% of sugar incorporation took place in pathway 2, and 10% or less in pathway 1, in human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast, approximately 50-90% of sugar incorporation took place in pathway 1 in C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14 times as much GSL as the other three cell lines. In C6 glioma cells, approximately 30% of sugar incorporation occurred in pathway 1 and 60% in pathway 2. There was no relation between the utilization of pathways for GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In both cells pathways 1 and 2 each accounted for 50% of incorporation of choline into sphingomyelin. In five of the six cell lines that we have studied, most GSL synthesis takes place in pathway 2. We suggest that when the need for synthesis is relatively low, as in slowly dividing cells, GSL are synthesized predominantly from sphingoid bases salvaged from the hydrolytic pathway. When cells are dividing more rapidly, the need for increased synthesis is met by upregulating the de novo pathway.

Carbohydrate Sequence↗
PubMed2006

The different ablation effects on atrioventricular nodal reentrant tachycardia in children with and without dual nodal pathways.

BACKGROUND: Previous studies in adults have shown a significant shortening of the fast pathway effective refractory period (ERP) after successful slow pathway ablation. However, information on atrioventricular nodal reentrant tachycardia (AVNRT) in children is limited. The purpose of this retrospective study was to investigate the different effects of radiofrequency (RF) catheter ablation in pediatric AVNRT patients between those with and without dual atrioventricular (AV) nodal pathways. METHODS: From January 1992 to August 2004, a total 67 pediatric patients with AVNRT underwent an electrophysiologic study and RF catheter ablation at our institution. We compared the electrophysiologic characteristics between those obtained before and after ablation in the children with AVNRT with and without dual AV nodal pathways. RESULTS: Dual AV nodal pathways were found in 37 (55%) of 67 children, including 36 (54%) with antegrade and 10 (15%) with retrograde dual AV nodal pathways. The antegrade and retrograde fast pathway ERPs in children with dual AV nodal pathways were both longer than the antegrade and retrograde ERPs in children without dual AV nodal pathways (300 +/- 68 vs 264 +/- 58 ms, P = 0.004; 415 +/- 70 vs 250 +/- 45 ms, P < 0.001) before ablation. In children with antegrade dual AV nodal pathways, the antegrade fast pathway ERP decreased from 300 +/- 68 ms to 258 +/- 62 ms (P = 0.008). The retrograde fast pathway ERP also decreased after successful ablation in the children with retrograde dual AV nodal pathways (415 +/- 70 vs. 358 +/- 72 ms, P = 0.026). CONCLUSION: The dual AV nodal physiology could not be commonly demonstrated in pediatric patients with inducible AVNRT. After a successful slow pathway ablation, the fast pathway ERP shortened significantly in the children with dual AV nodal pathways.

Adolescent↗
PubMed1987

Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes.

Our observations on the cellular immune response to type-A influenza suggest the existence of two distinct pathways of protein antigen presentation to T lymphocytes. One of these pathways is involved with presentation of antigens introduced into the presenting cell from without. This exogenous presentation pathway is the well-recognized route of presentation of soluble and particulate antigens to T lymphocytes. This pathway probably involves uptake of antigen into endocytic vesicles, alteration of antigen within an intracellular compartment, and subsequent display of antigen on the presenting cell surface (Unanue 1984). The second pathway is one which we have tentatively designated as an endogenous presentation pathway. The constraints on this pathway have yet to be fully defined. At a minimum, this pathway appears to involve the presentation of antigens which are synthesized de novo in the presenting cell utilizing the cell's biosynthetic machinery. This pathway may also handle preformed antigens located within the cytosolic compartment of the presenting cell. Perhaps the most striking feature of these two antigen presentation pathways is the close association between the MHC restriction of an antigen-specific T lymphocyte and the pathway of antigen presentation to that T lymphocyte. Our data suggest that this association holds both at the effector level and at the level of induction of T lymphocytes. Thus, presentation of a given antigen by the endogenous pathway preferentially triggers a response from class I MHC-restricted T lymphocytes directed to that antigen. The molecular basis for this link of class I MHC-restriction to the endogenous pathway and MHC class II restriction to the exogenous pathway is unknown. It seems likely that interactions between MHC molecules and antigen within the presenting cell may be critical for the demarcation of these pathways. Thus, for example, antigen presented by the endogenous route may only be able to associate intracellularly with newly synthesized or recycling class I MHC molecules. An understanding of the molecular basis of this phenomenon will require detailed information on the expression, intracellular trafficking, and transport of class I and class II MHC molecules in the antigen-presenting cell. An unresolved issue, at least in the case of viral antigens, is the nature and form of the antigenic moieties presented by the exogenous and endogenous pathways. In the case of viral antigen presentation to class II MHC-restricted T lymphocytes, there is strong, albeit indirect, evidence for processing of antigen and recognition of fragments of viral polypeptides (Lamb et al. 1982, Hackett et al. 1983).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Effect of capacitor size and pathway resistance on defibrillation threshold for implantable defibrillators.

BACKGROUND: The time constant of truncated exponential pulses used with implantable defibrillators is determined by the output capacitor size and defibrillation pathway resistance. The optimal capacitor size is unknown. METHODS AND RESULTS: This study compared defibrillation threshold (DFT) for standard 120-microF capacitors (DFT120) and smaller 60-microF capacitors (DFT60) at implantation of cardioverter-defibrillators in 67 patients using epicardial electrodes (15 patients) or one of four transvenous electrode configurations (52 patients). Paired comparisons of DFT60 and DFT120 were made for 44 defibrillation pathways using monophasic pulses and for 53 pathways using biphasic pulses. Truncated exponential pulses with 65% tilt were used. Pooled data from all electrode configurations showed a significant inverse correlation between pathway resistance and the ratio of stored energy DFT60 to DFT120 (monophasic pulses: r = .75, P = .0001; biphasic pulses: r = .68, P = .0001). Data from all electrode configurations formed a continuum with 120-microF capacitors superior for low-resistance pathways and 60-microF capacitors superior for high-resistance pathways. For pathways with resistance < or = 40 omega, the modest advantage of 120-microF capacitors applied primarily to pathways with low DFTs: 8.2 +/- 6.1 versus 9.6 +/- 5.4 J (P = .001) for monophasic pulses and 4.1 +/- 2.8 versus 5.1 +/- 3.1 J (P < .02) for biphasic pulses. The greater advantage of 60-microF capacitors for pathways with resistance > or = 61 omega applied to pathways with higher DFTs: 12.4 +/- 4.3 versus 23.1 +/- 6.4 J (P = .0001) for monophasic pulses and 8.5 +/- 4.9 versus 12.5 +/- 6.4 J (P = .0001) for biphasic pulses. For pathways using monophasic 120-microF pulses versus 95% for 60-microF pulses. Similarly, the DFT was < or = 10 J for 48% of pathways using biphasic 120-microF capacitors versus 83% for 60-microF pulses. CONCLUSIONS: In comparison with conventional 120-microF capacitors, 60-microF capacitors had clinically insignificant higher DFTs for low-resistance pathways and clinically important lower DFTs for high-resistance pathways. Optimal capacitance is inversely related to pathway resistance for clinical defibrillation pathways and waveforms.

Aged↗
PubMed2000

Expression patterns of glycoconjugates in the three distinctive olfactory pathways of the clawed frog, Xenopus laevis.

Xenopus laevis has three distinctive olfactory neuroepithelia. We examined the axonal projection from each of these epithelia to the olfactory bulb by Di-I labeling, and confirmed that the Xenopus primary olfactory pathways involve the dorsal pathway from the olfactory epithelium to the dorsal region of the main olfactory bulb, the ventral pathway from the middle chamber epithelium to the ventral region of the main olfactory bulb, and the vomeronasal pathway from the vomeronasal epithelium to the accessory olfactory bulb. We next examined expression patterns of glycoconjugates in the three olfactory pathways by lectin-histochemistry using 21 biotinylated lectins. Fourteen out of 21 lectins stained the Xenopus primary olfactory system. RCA-I stained the three olfactory pathways uniformly. PHA-E stained only the dorsal pathway. LEL, STL, PNA, ECL and UEA-I stained the dorsal pathway more intensely than the ventral pathway, and among them, only UEA-I stained the vomeronasal pathway. In contrast, s-WGA, DBA, SBA, BSL-I VVA, SJA and PHA-L showed intense stainings in the ventral pathway and moderate stainings in the vomeronasal pathway, but faint or weak stainings in the dorsal pathway. These observations suggest that the ventral pathway expresses glycoconjugates shared commonly with either the dorsal or the vomeronasal pathway. In addition, from the binding patterns of the lectins with a binding specificity for N-acetylgalactosamine, glycoconjugates containing this saccharide seem to play an important role for the organization of the olfactory pathways.

Affinity Labels↗
PubMed2003

A critical evaluation of critical pathways in head and neck cancer.

BACKGROUND: Critical pathways have been purported to decrease resource utilization in the management of head and neck cancer. Prior reports have documented shorter lengths of stay (LOS) for pathway patients than for historical cohorts. OBJECTIVE: To critically evaluate the impact of critical pathways on LOS after laryngectomy. DESIGN: Length-of-stay trends of 2 concurrent observational cohorts of laryngectomy patients (September 1992 to February 1999) were compared, 1 at each of 2 medical centers. One center instituted a critical pathway for laryngectomy patients in February 1997; the other never used such pathways. In addition, we examined the independent impact of the critical pathway at the pathway institution after controlling for date of laryngectomy (which reflected temporal trends) and other confounding variables. RESULTS: Both centers experienced reductions in LOS after February 1997, but there was no statistically significant difference between the reductions (1.9 days at the pathway center vs 1.5 days at the nonpathway center; P>.05). Multivariable linear and linear spline regression models demonstrated that the use of critical pathways at the pathway institution had no statistically significant impact on LOS after controlling for the date of laryngectomy. CONCLUSIONS: Pathway implementation has a limited direct impact on LOS in relatively low-volume procedures such as laryngectomy. Although pathways may influence utilization trends, their impact is likely mediated by the development and educational process that accompanies pathway adoption rather than implementation of the pathway itself. The inclusion of temporal trends and contemporary cohorts provides substantial insight into the effectiveness of critical pathways.

Aged↗
PubMedDate not supplied

Clinical pathway for pneumonia: development, implementation, and initial experience.

BACKGROUND: As part of a large multidisciplinary project to reduce cost, decrease hospital length of stay, and improve efficiency of patient care at Saint Mary's Hospital, a clinical pathway for pneumonia was developed and implemented. METHODS: After using analysis of severity-adjusted data to determine which conditions would be best targets for improvement, a utilization management steering committee created a multidisciplinary group to develop a clinical pathway for pneumonia. This group was led by physician champions and consisted of representatives from nursing, respiratory therapy, pharmacy, and home healthcare. With information gained from chart abstraction, which identified "best practice" patterns, guidance from the medical literature, and local expertise, this group developed a clinical pathway that included an auxiliary protocol for respiratory care and a detailed educational brochure for patients. Before implementing the clinical pathway, extensive educational activities were undertaken involving the medical staff, house staff, nurses, and other staff. Data collected on consecutive patients discharged after implementation of the pathway were compared with data collected on patients discharged before the pathway in 1994. RESULTS: For DRG 89, the patients who were on the pathway in comparison to the control patients from 1994 had a lower average length of stay by 1.45 days (5.84 vs. 7.29 days) and a lower average total charge by $1,453 ($9,511 vs. $10,964). For DRG 90, the patients who were on the pathway in comparison to the control patients from 1994 had a lower average length of stay by 1.83 days (3.45 vs. 5.28 days) and a lower average total charge by $1319 ($5450 vs. $6769). CONCLUSIONS: The pneumonia clinical pathway that was implemented was associated with reductions in the length of stay and total charges. These reductions were seen in relationship to historical controls and to patients cared for concurrently who were not placed on the pathway. Although not fully used on all pneumonia patients, the presence of the pathway probably had some positive effects even on patients not formally on the pathway, through systems changes and educational influences. The pathway also positively influenced other conditions by the use of ancillary algorithms for conditions other than pneumonia, and the more rapid administration of antibiotics for other infectious diseases. Also, lessons learned in the creation of this first pathway have been helpful in streamlining the process of future pathway development.

Connecticut↗
PubMed1994

Atrial and accessory pathway activation direction in patients with orthodromic supraventricular tachycardia: insights from vector mapping.

OBJECTIVES: The purpose of this study was to utilize vector mapping to investigate atrial and accessory pathway activation direction during orthodromic supraventricular tachycardia. BACKGROUND: Although advances have been made in the electrophysiologic evaluation and management of accessory pathways, our understanding of accessory pathway anatomy and physiology remains incomplete. Vector mapping has been validated as a method of studying local myocardial activation. METHODS: In 28 patients with a left-sided or posteroseptal accessory atrioventricular (AV) pathway referred for ablation, atrial and accessory AV pathway activation direction was determined during ventricular pacing or orthodromic supraventricular tachycardia, or both, by summing three orthogonally oriented bipolar electrograms recorded from the coronary sinus to create three-dimensional vector loops. Atrial and accessory AV pathway activation direction was determined in all patients from the maximal amplitude vectors of the vector loops. Because of beat to beat variability in the directions of the vector loops, data from 8 of 28 patients could not be analyzed. RESULTS: At 81 of 83 sites, atrial activation direction along the long axis of the coronary sinus corresponded with the direction suggested by activation time mapping. Activation direction along the anteroposterior and inferosuperior axes was variable, potentially due to variations in the level of the atrial insertion of the accessory AV pathway and in the depth or angling of pathway fibers in the AV fat pad. In eight patients, at least one recording was obtained at the site of an accessory AV pathway potential. Accessory AV pathway activation proceeded superiorly and to the right in seven of eight patients; in one patient with a posteroseptal pathway, accessory AV pathway activation proceeded superiorly and to the left. CONCLUSIONS: 1) Vector mapping is a useful technique for localizing accessory AV pathways; 2) left-sided accessory AV pathways angle from left to right as they traverse the AV groove; and 3) variable activation directions of the atrial myocardium adjacent to the coronary sinus suggest that accessory AV pathway insertion into the atrium differs from patient to patient.

Adult↗
PubMed1996

Posterior fast atrioventricular node pathways: implications for radiofrequency catheter ablation of atrioventricular node reentrant tachycardia.

OBJECTIVES: This study sought to present evidence that fast atrioventricular (AV) node pathways with posterior exit sites may participate in typical AV node reentry. BACKGROUND: Catheter ablation of the slow AV node pathway in the posteroseptal right atrium is the preferred therapeutic approach in patients with AV node reentrant tachycardia. Despite the success achieved with this approach, electrophysiologic changes consistent with fast pathway ablation are occasionally observed. One potential explanation is the presence of an aberrant posterior fast pathway. METHODS: The location of fast and slow AV node pathways was determined by atrial activation mapping along the tricuspid valve annulus during tachycardia and was further confirmed by the effect of radiofrequency catheter ablation. RESULTS: Seven patients with AV node reentrant tachycardia had evidence of a posterior fast pathway near the coronary sinus os. Abolition of anterograde and retrograde fast pathway conduction followed radiofrequency ablation in the posteroseptal region in six patients. Consistent with fast pathway ablation, the AH interval increased from 70 +/- 24 to 195 +/- 35 ms (mean +/- SD), and tachycardia was no longer inducible. Selective slow pathway ablation was performed in one other patient with a posterior fast pathway. CONCLUSIONS: Functionally fast AV node pathways may be located in the posteroseptal right atrium, where slow pathway modification is performed. These data delineate the limitation of an anatomically guided slow pathway ablative approach and emphasize the importance of detailed mapping and localization of the retrograde fast pathway exit site before ablation. Failure to recognize the presence of posterior fast AV node pathways may account for sporadic examples of AV block, complicating posteroseptal ablation in patients with AV node reentry.

Adult↗
PubMed2004

A computational approach to measuring coherence of gene expression in pathways.

This study uses a computational approach to analyze coherence of expression of genes in pathways. Microarray data were analyzed with respect to coherent gene expression in a group of genes defined as a pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Our hypothesis is that genes in the same pathway are more likely to be coordinately regulated than a randomly selected gene set. A correlation coefficient for each pair of genes in a pathway was estimated based on gene expression in normal or tumor samples, and statistically significant correlation coefficients were identified. The coherence indicator was defined as the ratio of the number of gene pairs in the pathway whose correlation coefficients are significant, divided by the total number of gene pairs in the pathway. We defined all genes that appeared in the KEGG pathways as a reference gene set. Our analysis indicated that the mean coherence indicator of pathways is significantly larger than the mean coherence indicator of random gene sets drawn from the reference gene set. Thus, the result supports our hypothesis. The significance of each individual pathway of n genes was evaluated by comparing its coherence indicator with coherence indicators of 1000 random permutation sets of n genes chosen from the reference gene set. We analyzed three data sets: two Affymetrix microarrays and one cDNA microarray. For each of the three data sets, statistically significant pathways were identified among all KEGG pathways. Seven of 96 pathways had a significant coherence indicator in normal tissue and 14 of 96 pathways had a significant coherence indicator in tumor tissue in all three data sets. The increase in the number of pathways with significant coherence indicators may reflect the fact that tumor cells have a higher rate of metabolism than normal cells. Five pathways involved in oxidative phosphorylation, ATP synthesis, protein synthesis, or RNA synthesis were coherent in both normal and tumor tissue, demonstrating that these are essential genes, a high level of expression of which is required regardless of cell type.

Databases, Genetic↗
PubMed1997

Similar time-dependent recovery property of fast and slow atrioventricular nodal pathways.

The purpose of this study was to determine whether fast and slow atrioventricular (AV) nodal pathways have the same recovery property. AV nodal recovery property is studied by delivering atrial extrastimuli coupled to atrial beats and plotting nodal coupling intervals against nodal conduction time. In patients with dual pathways the resultant curves will include a fast to fast (F-F) and a fast to slow (F-S) pathway coupled curves. Although fast pathway recovery property can be represented by the former, slow pathway recovery property requires further assessment by studying slow to slow (S-S) pathways coupled curve. In 9 patients with dual pathways F-F, F-S, S-F, and S-S curves were obtained by pacing protocols. In 8 patients (control) without dual pathways, F-F curve and atrial extrastimuli coupled to a preceding slowly conducted fast pathway beat (also designated as S-F curve) were obtained. (1) The S-S curve had a similar time constant as the F-F curve. (2) Although the S-S curve was markedly shifted upward and leftward from the F-F curve, the degree of leftward and upward shifts of the S-S curve from the F-F curve were both close to the difference of the basic fast and slow pathway conduction time (a constant). (3) Although the effective refractory period of the fast pathway in dual pathway patients was longer than that of the control patients, the slow pathway effective refractory period when corrected was close to that of fast pathway in control patients. These results suggest that the fast and slow AV nodal pathways have a similar time-dependent recovery property.

Adolescent↗