SEARCH · PubMed Health

Results for “pathways”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed2006

Pathway and gene-set activation measurement from mRNA expression data: the tissue distribution of human pathways.

BACKGROUND: Interpretation of lists of genes or proteins with altered expression is a critical and time-consuming part of microarray and proteomics research, but relatively little attention has been paid to methods for extracting biological meaning from these output lists. One powerful approach is to examine the expression of predefined biological pathways and gene sets, such as metabolic and signaling pathways and macromolecular complexes. Although many methods for measuring pathway expression have been proposed, a systematic analysis of the performance of multiple methods over multiple independent data sets has not previously been reported. RESULTS: Five different measures of pathway expression were compared in an analysis of nine publicly available mRNA expression data sets. The relative sensitivity of the metrics varied greatly across data sets, and the biological pathways identified for each data set are also dependent on the choice of pathway activation metric. In addition, we show that removing incoherent pathways prior to analysis improves specificity. Finally, we create and analyze a public map of pathway expression in human tissues by gene-set analysis of a large compendium of human expression data. CONCLUSION: We show that both the detection sensitivity and identity of pathways significantly perturbed in a microarray experiment are highly dependent on the analysis methods used and how incoherent pathways are treated. Analysts should thus consider using multiple approaches to test the robustness of their biological interpretations. We also provide a comprehensive picture of the tissue distribution of human gene pathways and a useful public archive of human pathway expression data.

Cell Line↗

PubMed1994

Radiofrequency catheter ablation of atrioventricular accessory pathways in Wolff-Parkinson-White syndrome with drug-refractory and symptomatic supraventricular tachycardia--its high effectiveness irrespective of accessory pathway location and properties.

Radiofrequency catheter ablation of atrioventricular accessory pathways was performed in 125 cases of the Wolff-Parkinson-White syndrome (type-A:54, type-B: 29, concealed: 42) complicated with drug-refractory and symptomatic atrioventricular reentrant tachycardia and/or paroxysmal atrial fibrillation. A total of 135 accessory pathways were identified: 50 left free-wall manifest, 34 left free-wall concealed, 21 right free-wall manifest, 2 right free-wall concealed, 15 posteroseptal manifest, 10 posteroseptal concealed, 2 right anteroseptal manifest and 1 right anteroseptal concealed. Accessory pathway conduction was successfully eliminated in 133 of these 135 accessory pathways (99%). Two right posteroseptal pathways were eventually ablated with direct current. Successful ablation required a mean 5.2 applications of radiofrequency current, a mean total energy of 2615 J and a mean fluoroscopic time of 52 min. The mean number of applications, applied energy and fluoroscopic time were greater in the right free-wall pathways than in the left free-wall pathways, and in the concealed pathways than in the manifest pathways. None of the procedures produced complications. During a mean follow-up period of 11.5 months, 1 right free-wall accessory pathway recurred and was ablated successfully in a repeat session. These results suggest that radiofrequency catheter ablation of accessory pathways is highly effective and safe irrespective of the accessory pathway location and properties, although these factors can affect the difficulty of this procedure. This technique may be an alternative to surgical therapy for Wolff-Parkinson-White syndrome with drug-refractory and symptomatic supraventricular tachyarrhythmias.

Adolescent↗

PubMed2002

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.

The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway. Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S. pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation. These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.

Animals↗

PubMed2004

The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation.

Complement activation with formation of biologically potent mediators like C5a and the terminal C5b-9 complex (TCC) contributes essentially to development of inflammation and tissue damage in a number of autoimmune and inflammatory conditions. A particular role for complement in the ischaemia/reperfusion injury of the heart, skeletal muscle, central nervous system, intestine and kidney has been suggested from animal studies. Previous experiments in C3 and C4 knockout mice suggested an important role of the classical or lectin pathway in initiation of complement activation during intestinal ischaemia/reperfusion injury while later use of factor D knockout mice showed the alternative pathway to be critically involved. We hypothesized that alternative pathway amplification might play a more critical role in classical pathway-induced C5 activation than previously recognized and used pathway-selective inhibitory mAbs to further elucidate the role of the alternative pathway. Here we demonstrate that selective blockade of the alternative pathway by neutralizing factor D in human serum diluted 1 : 2 with mAb 166-32 inhibited more than 80% of C5a and TCC formation induced by solid phase IgM and solid- and fluid-phase human aggregated IgG via the classical pathway. The findings emphasize the influence of alternative pathway amplification on the effect of initial classical pathway activation and the therapeutic potential of inhibiting the alternative pathway in clinical conditions with excessive and uncontrolled complement activation.

Antibodies, Monoclonal↗

PubMed2003

Anterograde slow pathway is not the same as retrograde slow pathway conducted in the reverse direction in patients with uncommon atrioventricular nodal reentrant tachycardia.

INTRODUCTION: The aim of this study was to examine the location of anterograde and retrograde slow pathways in 16 patients with uncommon atrioventricular nodal reentrant tachycardia (AVNRT), including the fast-slow form in 10, slow-slow form in 5, and both fast-slow and slow-slow forms in 1. METHODS AND RESULTS: Patients were divided into two groups according to the approach used for slow pathway ablation in the initial radiofrequency catheter ablation (RFCA): one approach used earliest atrial activation during tachycardia (ES group, n = 9), and the other used a slow potential during sinus rhythm (SP group, n = 7). When the initial RFCA failed to eliminate slow pathway conduction in the ES group, an additional RFCA guided by a slow potential was performed. The ratio of lengths from the His-bundle region to the RFCA site and coronary sinus ostium (Abl/His-CS ratio) and the ratio of amplitudes of atrial and ventricular potentials at the RFCA site (A/V ratio) were compared between the two groups. In the initial RFCA, retrograde slow pathway conduction was eliminated without impairment of anterograde slow pathway conduction in 8 (89%) patients from the ES group, and bidirectional slow pathway conduction was eliminated in 6 (86%) patients from the SP group. Residual anterograde slow pathway conduction that was preserved after the initial RFCA in 8 of 9 patients was eliminated by an additional slow potential-guided RFCA. Both the Abl/His-CS ratio (0.86 +/- 0.07 vs 0.73 +/- 0.11, P = 0.01) and A/V ratio (0.80 +/- 0.31 vs. 0.14 +/- 0.01, P < 0.001) were higher in the ES group than the SP group. The ratios for the residual anterograde slow pathway ablation in the ES group were similar to those in the SP group. CONCLUSION: The results of this study suggest that the retrograde slow pathway runs more on the atrial side of the tricuspid valve annulus at the level of the coronary sinus ostium compared with the anterograde slow pathway, although both pathways run parallel or are fused in portions more proximal to the His bundle.

Adult↗

PubMedDate not supplied

An interdisciplinary, evidence-based process of clinical pathway implementation increases pathway usage.

Clinical pathways have been implemented in many healthcare settings as a link between evidence and practice. Most published research concludes that when clinical pathways are implemented and used by health professionals, there is a positive impact on health outcomes. However, some research also suggests that utilization of clinical pathways by health professionals is low and that implementation strategies for linking evidence with clinical practice often prove to be weak or ineffective. This paper describes a before and after study to determine whether an interdisciplinary, genuinely collaborative, and evidence-based process of clinical pathway implementation resulted in increased documented use of an acute myocardial infarction (AMI) clinical pathway by health professionals in a regional Australian hospital. Underpinning the design and implementation process was the belief that true team involvement would lead to ownership, acceptance, and, ultimately, to increased usage of the pathway. Documented clinical pathway usage was measured in two ways: (1) the presence of the AMI clinical pathway in the medical records of patients diagnosed with an AMI and (2) the proportion of the AMI clinical pathway completed when it was present in the medical record. A total of 195 medical records of those diagnosed with an AMI were audited before (n = 124) and after (n = 71) the implementation process. The interdisciplinary, truly collaborative, and evidence-based implementation process resulted in a statistically significant increase in documented usage of the AMI pathway (22.6% vs. 57.7%; p <.000). Results indicate that involvement of key users in the design and implementation of a clinical pathway significantly increases staff utilization of the document.

Aged↗

PubMed2004

Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness.

Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of on-pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the off-pathway remained active. Both CSNB1-NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The off-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific on-pathway signaling deficiency in CSNB1-NYX males with no evidence of off-pathway involvement. Likewise, rapid-on/off ramping stimuli also indicated that the functional deficit was localized to the on pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to on/off-pathway contributions to ramping on/off ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the on pathway at the level of depolarizing bipolar cells, and thus human CSNB1-NYX subjects provide an opportunity to probe the primate visual system for consequences of on-pathway deficits.

Adolescent↗

PubMed2000

1alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 and 1alpha,25-dihydroxy-16-ene-23-yne-20-epi-vitamin D3: analogs of 1alpha,25-dihydroxyvitamin D3 that resist metabolism through the C-24 oxidation pathway are metabolized through the C-3 epimerization pathway.

The secosteroid hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is metabolized in its target tissues through modifications of both the side chain and the A-ring. The C-24 oxidation pathway, the previously well established main side chain modification pathway, is initiated by hydroxylation at C-24 of the side chain. The C-3 epimerization pathway, the newly discovered A-ring modification pathway, is initiated by epimerization of the hydroxyl group at C-3 of the A-ring. The end products of the metabolism of 1alpha,25(OH)2D3 through the C-24 oxidation and the C-3 epimerization pathways are calcitroic acid and 1alpha,25-dihydroxy-3-epi-vitamin-D3 respectively. During the past two decades, numerous noncalcemic analogs of 1alpha,25(OH)2D3 were synthesized. Several of the analogs have altered side chain structures and as a result some of these analogs have been shown to resist their metabolism through side chain modifications. For example, two of the analogs, namely, 1alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 [1alpha,25(OH)2-16-ene-23-yne-D3] and 1alpha,25-dihydroxy-16-ene-23-yne-20-epi-vitamin D3 [1alpha,25(OH)2-16-ene-23-yne-20-epi-D3], have been shown to resist their metabolism through the C-24 oxidation pathway. However, the possibility of the metabolism of these two analogs through the C-3 epimerization pathway has not been studied. Therefore, in our present study, we investigated the metabolism of these two analogs in rat osteosarcoma cells (UMR 106) which are known to express the C-3 epimerization pathway. The results of our study indicate that both analogs [1alpha,25(OH)2-16-ene-23-yne-D3 and 1alpha,25(OH)2-16-ene-23-yne-20-epi-D3] are metabolized through the C-3 epimerization pathway in UMR 106 cells. The identity of the C-3 epimer of 1alpha,25(OH)2-16-ene-23-yne-D3 [1alpha,25(OH)2-16-ene-23-yne-3-epi-D3] was confirmed by GC/MS analysis and its comigration with synthetic 1alpha,25(OH)2-16-ene-23-yne-3-epi-D3 on both straight and reverse-phase HPLC systems. The identity of the C-3 epimer of 1alpha,25(OH)2-16-ene-23-yne-20-epi-D3 [1alpha,25(OH)2-16-ene-23-yne-20-epi-3-epi-D3] was confirmed by GC/MS and 1H NMR analysis. Thus, we indicate that vitamin D analogs which resist their metabolism through the C-24 oxidation pathway, have the potential to be metabolized through the C-3 epimerization pathway. In our present study, we also noted that the rate of C-3 epimerization of 1alpha,25(OH)2-16-ene-23-yne-20-epi-D3 is about 10 times greater than the rate of C-3 epimerization of 1alpha,25(OH)2-16-ene-23-yne-D3. Thus, we indicate for the first time that certain structural modifications of the side chain such as 20-epi modification can alter significantly the rate of C-3 epimerization of vitamin D compounds.

Animals↗

PubMed2000

Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective.

Cellular metabolism is most often described and interpreted in terms of the biochemical reactions that make up the metabolic network. Genomics is providing near complete information regarding the genes/gene products participating in cellular metabolism for a growing number of organisms. As the true functional units of metabolic systems are its pathways, the time has arrived to define metabolic pathways in the context of whole-cell metabolism for the analysis of the structural design and capabilities of the metabolic network. In this study, we present the theoretical foundations for the identification of the unique set of systemically independent biochemical pathways, termed extreme pathways, based on system stochiometry and limited thermodynamics. These pathways represent the edges of the steady-state flux cone derived from convex analysis, and they can be used to represent any flux distribution achievable by the metabolic network. An algorithm is presented to determine the set of extreme pathways for a system of any complexity and a classification scheme is introduced for the characterization of these pathways. The property of systemic independence is discussed along with its implications for issues related to metabolic regulation and the evolution of cellular metabolic networks. The underlying pathway structure that is determined from the set of extreme pathways now provides us with the ability to analyse, interpret, and perhaps predict metabolic function from a pathway-based perspective in addition to the traditional reaction-based perspective. The algorithm and classification scheme developed can be used to describe the pathway structure in annotated genomes to explore the capabilities of an organism.

Algorithms↗

PubMed1990

Retrograde dual atrioventricular nodal pathway in patients with atrioventricular reciprocating tachycardia using concealed accessory pathways.

We present electrophysiological studies in two patients with atrioventricular reciprocating tachycardias. The first patient had anterograde dual atrioventricular nodal pathways with a right-sided concealed accessory pathway. The retrograde atrioventricular nodal pathway showed evidence suggestive of slow pathway properties. After block was induced with ajmaline in the accessory pathway, a typical pattern of discontinuous retrograde atrioventricular nodal conduction curves was recognized. We then observed three types of induced atrioventricular reentry. The other patient had continuous anterograde atrioventricular nodal conduction, a fast-conducting retrograde atrioventricular nodal pathway and a left-sided concealed accessory pathway. After refractoriness had been induced in the accessory pathway with ajmaline, a typical pattern of retrograde dual atrioventricular nodal pathways was recognized, and it proved impossible to induce atrioventricular nodal echoes. Induction of block or impairment of conduction with ajmaline in the concealed accessory pathway proved helpful in the disclosure of retrograde dual atrioventricular nodal pathways by means of the ventricular extrastimulus method.

Adolescent↗

PubMed1992

Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location.

OBJECTIVES: This study was designed to assess the influence of accessory atrioventricular (AV) pathway location on the clinical and electrophysiologic characteristics of 384 consecutive symptomatic patients having a single accessory pathway. METHODS: Four locations were studied: left free wall (n = 270), posteroseptal (n = 52), anteroseptal (n = 29) and right free wall (n = 33). Ten clinical variables and 12 electrophysiologic variables were analyzed, including the effective refractory period of the accessory pathway and the different clinically occurring and inducible arrhythmias. RESULTS: Only two clinical findings were associated with accessory pathway location: 1) later age at onset of symptoms in the left free wall versus other accessory pathway locations (24 +/- 12 vs. 20 +/- 11 years, p = 0.02), and 2) later age at the time of electrophysiologic study in the left free wall accessory pathway location (36 +/- 13 vs. 32 +/- 11 years, p = 0.01). Six electrophysiologic variables showed a correlation with the accessory pathway location: 1) retrograde conduction only was found less frequently in right free wall (9%) and anteroseptal (10%) than in left free wall (26%) and posteroseptal (29%) accessory pathway locations (p = 0.05); 2) the retrograde effective refractory period of the accessory pathway was shorter in anteroseptal (253 +/- 52 ms) and left free wall (270 +/- 72 ms) as compared with right free wall (296 +/- 101 ms) and posteroseptal (301 +/- 76 ms) locations (p = 0.05); 3) retrograde decremental conduction over the accessory pathway was present in the posteroseptal (17%) and left free wall (3%) but absent in the other locations (p less than 0.001); 4) anterograde decremental conduction was only seen in the right free wall location (12%) (p less than 0.001); 5) orthodromic reentrant tachycardia was induced less frequently in the right free wall than in other locations (70% vs. 93%, p less than 0.001); and 6) inducibility of atrial fibrillation was greater in anteroseptal (62%) than in right free wall (21%), left free wall (44%) and posteroseptal (36%) locations (p = 0.01). CONCLUSIONS: The location of the accessory AV pathway is associated with specific electrophysiologic characteristics.

Adolescent↗

PubMed2005

Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity.

A novel in vivo method of producing succinate has been developed. A genetically engineered Escherichia coli strain has been constructed to meet the NADH requirement and carbon demand to produce high quantities and yield of succinate by strategically implementing metabolic pathway alterations. Currently, the maximum theoretical succinate yield under strictly anaerobic conditions through the fermentative succinate biosynthesis pathway is limited to one mole per mole of glucose due to NADH limitation. The implemented strategic design involves the construction of a dual succinate synthesis route, which diverts required quantities of NADH through the traditional fermentative pathway and maximizes the carbon converted to succinate by balancing the carbon flux through the fermentative pathway and the glyoxylate pathway (which has less NADH requirement). The synthesis of succinate uses a combination of the two pathways to balance the NADH. Consequently, experimental results indicated that these combined pathways gave the most efficient conversion of glucose to succinate with the highest yield using only 1.25 moles of NADH per mole of succinate in contrast to the sole fermentative pathway, which uses 2 moles of NADH per mole of succinate. A recombinant E. coli strain, SBS550MG, was created by deactivating adhE, ldhA and ack-pta from the central metabolic pathway and by activating the glyoxylate pathway through the inactivation of iclR, which encodes a transcriptional repressor protein of the glyoxylate bypass. The inactivation of these genes in SBS550MG increased the succinate yield from glucose to about 1.6 mol/mol with an average anaerobic productivity rate of 10 mM/h (approximately 0.64 mM/h-OD600). This strain is capable of fermenting high concentrations of glucose in less than 24 h. Additional derepression of the glyxoylate pathway by inactivation of arcA, leading to a strain designated as SBS660MG, did not significantly increase the succinate yield and it decreased glucose consumption by 80%. It was also observed that an adhE, ldhA and ack-pta mutant designated as SBS990MG, was able to achieve a high succinate yield similar to SBS550MG when expressing a Bacillus subtilis NADH-insensitive citrate synthase from a plasmid.

Anaerobiosis↗

PubMed2001

Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway.

The cAMP-responsive element binding protein (CREB), a key regulator of gene expression, is activated by phosphorylation on Ser-133. Several different protein kinases possess the capability of driving this phosphorylation, making it a point of potential convergence for multiple intracellular signaling cascades. Previous work in neurons has indicated that physiologic synaptic stimulation recruits a fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early signaling to CREB. Here we show in hippocampal neurons that the fast, CaMK-dependent pathway can be followed by a slower pathway that depends on Ras/mitogen-activated protein kinase (MAPK), along with CaMK. This pathway was blocked by dominant-negative Ras and was specifically recruited by depolarizations that produced strong intracellular Ca(2+) transients. When both pathways were recruited, phosphorylated CREB (pCREB) formation was overwhelmingly dominated by the CaMK pathway between 0 and 10 min, and by the MAPK pathway at 60 min, whereas the two pathways acted in concert at 30 min. The Ca(2+) signals that produced only rapid CaMK signaling to pCREB or both rapid CaMK and slow MAPK signaling deviated significantly for only approximately 1 min, yet their differential impact on pCREB extended over a much longer period, between 20 and 60 min and beyond, which is of likely significance for gene expression. The CaMK-dependent MAPK pathway may inform the nucleus about stimulus amplitude. In contrast, the CaMKIV pathway may be well suited to conveying information on the precise timing of localized synaptic stimuli, befitting its greater speed and sensitivity, whereas the previously described calcineurin pathway may carry information about stimulus duration.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1994

Shortening of fast pathway refractoriness after slow pathway ablation. Effects of autonomic blockade.

BACKGROUND: Shortening of the anterograde effective refractory period (ERP) of the fast pathway has been reported after radiofrequency ablation of the slow pathway. We hypothesized that ERP shortening may be related to autonomic changes, possibly catecholamine release, as a result of ablation. METHODS AND RESULTS: To test this, 10 consecutive patients with atrioventricular node reentry undergoing slow pathway ablation were given autonomic blockade before the ablation procedure. This was achieved by atropine 0.03 mg/kg and propranolol 0.15 mg/kg IV supplemented by half the initial dose after ablation and before the final study. A control group of 10 patients underwent the protocol without autonomic blockade. Before ablation, autonomic blockade did not alter the ERP of either the fast pathway (295 +/- 22 versus 298 +/- 26 milliseconds) or the slow pathway (264 +/- 36 versus 269 +/- 38 milliseconds). Autonomic blockade obscured dual pathway physiology in 2 patients and brought it out in another 2 without dual pathway physiology initially. Slow pathway ablation shortened the ERP of the fast pathway for the group as a whole (331.5 +/- 54 versus 305.5 +/- 60 milliseconds, mean +/- SD, n = 20, P < .04). There was no difference in degree of ERP shortening in control patients (23.5 +/- 58 milliseconds) or autonomic blockade patients (25.5 +/- 52 milliseconds). CONCLUSIONS: These data suggest that shortening of the ERP of the fast pathway after slow pathway ablation is not mediated by autonomic changes.

Adult↗

PubMed2003

Reducing clinical variations with clinical pathways: do pathways work?

OBJECTIVE: To test clinical pathways in a variety of Italian health care organizations in 2000-2002 to measure performance in decreasing process and outcome variations. DESIGN: Creation of indicators, specific for each clinical pathway, to measure variations in the care processes and outcomes. Pre- and post-analysis model to evaluate the possible effect of the clinical pathways on each indicator. SETTING: We tested the clinical pathways in six sites, each with different clinical pathways. RESULTS: Reductions in health care macro-variation phenomena (length of stay, patient pathways, etc.) and in performance micro-variation (variations in diagnostic and therapeutic prescriptions, protocol implementation, etc.) were shown in sites where pathways were implemented successfully. A significant improvement in outcome for patients who were treated according to the clinical pathway for heart failure was also demonstrated. CONCLUSIONS: The overall purpose of clinical pathways is to improve outcome by providing a mechanism to coordinate care and to reduce fragmentation, and ultimately cost. Our results demonstrated that it is possible to achieve this goal. Although controversial elements still exist, we think that clinical pathways can have a positive impact on quality in health care.

Aged↗

PubMed1998

Clinical and electrophysiologic characteristics and long-term efficacy of slow-pathway catheter ablation in patients with spontaneous supraventricular tachycardia and dual atrioventricular node pathways without inducible tachycardia.

OBJECTIVES: We sought to investigate the long-term efficacy of slow-pathway catheter ablation in patients with spontaneous, documented paroxysmal supraventricular tachycardia (PSVT) and dual atrioventricular (AV) node pathways but without inducible tachycardia. BACKGROUND: The lack of reproduction of clinical PSVT by programmed electrical stimulation, which is not uncommon in AV node reentrant tachycardia (AVNRT), is a dilemma in making the decision of the therapeutic end point of radiofrequency catheter ablation. METHODS: Twenty-seven patients (group A) with documented but noninducible PSVT and with dual AV node pathways were prospectively studied. Programmed electrical stimulation could induce a single AV node echo beat in 12 patients, double echo beats in 4 patients and none in 11 patients at baseline or during isoproterenol infusion. Of the patients in group A, 16 underwent slow-pathway catheter ablation and 11 did not. The clinical and electrophysiologic characteristics of the 27 patients were compared with those of patients with dual AV node pathways and inducible AVNRT (group B, n = 55) and patients with dual AV node pathways alone without clinical PSVT (group C, n = 47). RESULTS: During 23+/-13 months of follow-up, none of the 16 patients with slow-pathway catheter ablation had recurrence of PSVT. However, 7 of the 11 patients without ablation had PSVT recurrence at 13+/-14 months of follow-up (p < 0.03 by Kaplan-Meier analysis). Compared with groups B and C, group A consisted predominantly of men who had better retrograde AV node conduction and a narrower zone for anterograde slow-pathway conduction. CONCLUSIONS: Slow-pathway catheter ablation is highly effective in eliminating spontaneous PSVT in which the tachycardia is not inducible despite the presence of dual AV node pathways.

Adolescent↗

PubMed1999

Developmental pathways to antisocial behavior: the delayed-onset pathway in girls.

Recent research has suggested that there are two distinct trajectories for the development of antisocial behavior in boys: a childhood-onset pathway and an adolescent-onset pathway. After reviewing the limited available research on antisocial girls, we propose that this influential method of conceptualizing the development of severe antisocial behavior may not apply to girls without some important modifications. Antisocial girls appear to show many of the correlates that have been associated with the childhood-onset pathway in boys, and they tend to show impaired adult adjustment, which is also similar to boys in the childhood-onset pathway. However, antisocial girls typically show an adolescent-onset to their antisocial behavior. We have proposed that these girls show a third developmental pathway which we have labeled the "delayed-onset" pathway. This model rests on the assumption that many of the putative pathogenic mechanisms that contribute to the development of antisocial behavior in girls, such as cognitive and neuropsychological deficits, a dysfunctional family environment, and/or the presence of a callous and unemotional interpersonal style, may be present in childhood, but they do not lead to severe and overt antisocial behavior until adolescence. Therefore, we propose that the delayed-onset pathway for girls is analogous to the childhood-onset pathway in boys and that there is no analogous pathway in girls to the adolescent-onset pathway in boys. Although this model clearly needs to be tested in future research, it highlights the need to test the applicability of current theoretical models for explaining the development of antisocial behavior in girls.

Adolescent↗

PubMed1969

The pentose phosphate pathway of glucose metabolism. Enzyme profiles and transient and steady-state content of intermediates of alternative pathways of glucose metabolism in Krebs ascites cells.

1. The pentose phosphate pathway in Krebs ascites cells was investigated for regulatory reactions. For comparison, the glycolytic pathway was studied simultaneously. 2. Activities of the pentose phosphate pathway enzymes were low in contrast with those of the enzymes of glycolysis. The K(m) values of glucose 6-phosphate dehydrogenase for both substrate and cofactor were about four times the reported upper limit for the enzyme from normal tissues. Fructose 1,6-diphosphate and NADPH competitively inhibited 6-phosphogluconate dehydrogenase. 3. About 28% of the hexokinase activity was in the particulate fraction of the cells. The soluble enzyme was inhibited by fructose 1,6-diphosphate and ribose 5-phosphate, but not by 3-phosphoglycerate. The behaviour of the partially purified soluble enzyme in vitro in a system simulating the concentrations of ATP, glucose 6-phosphate and P(i) found in vivo is reported. 4. Kinetics of metabolite accumulation during the transient state after the addition of glucose to the cells indicated two phases of glucose phosphorylation, an initial rapid phase followed abruptly by a slow phase extending into the steady state. 5. Of the pentose phosphate pathway intermediates, accumulation of 6-phosphogluconate, sedoheptulose 7-phosphate and fructose 6-phosphate paralleled the accumulation of glucose 6-phosphate. Erythrose 4-phosphate reached the steady-state concentration by 2min., whereas the pentose phosphates accumulated linearly. 6. The mass-action ratios of the pentose phosphate pathway reactions were calculated. The transketolase reaction was at equilibrium by 30sec. and then progressively shifted away from equilibrium towards the steady-state ratio. The glucose 6-phosphate dehydrogenase was far from equilibrium at all times. 7. Investigation of the flux of [(14)C]glucose carbon confirmed the existence of an operative pentose phosphate pathway in ascites cells, contributing 1% of the total flux in control cells and 10% in cells treated with phenazine methosulphate. 8. The pentose phosphate formed by way of the direct oxidative route and estimated from the (14)CO(2) yields represented 20% of the total accumulated pentose phosphate, the other 80% being formed by the non-oxidative reactions of the pentose phosphate pathway. 9. The pentose phosphate pathway appears to function as two separate pathways, both operating towards pentose phosphate formation. Control of the two pathways is discussed.

Adenosine Triphosphate↗