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PubMed1997

Defibrillation efficacy using high-frequency switching to proportion current among simultaneous shock pathways.

INTRODUCTION: Multiple-pathway electrode configurations generally allow improved current distribution over the heart and lower defibrillation thresholds than single-pathway systems. However, current distributions using multiple pathways are largely determined by electrode type and location. We hypothesized that switching the current among multiple pathways at high frequency (HF) could allow the switching duty cycle to control the proportion of time-averaged current flowing in each pathway, thus permitting altered (possibly improved) defibrillation efficacy using the same electrodes and shock waveform. METHODS AND RESULTS: In dogs, we measured the current (I50) for 50% defibrillation success using catheter electrodes in the right ventricular apex (cathode) and superior vena cava (A-pathway anode) and a subcutaneous patch on the left chest wall (B-pathway anode). In group 1 (N = 7), we measured I50s for shocks that used HF to proportion 10% to 90% of the current to the A-pathway. Shocks with 10% to 30% of the current in the A-pathway had significantly lowr I50s than nonproportioned shocks using all three electrodes. However, the resistance differed among single and simultaneous pathways so energy did not necessarily parallel these changes. In group 2 (N = 6), we measured I50s for shocks to the B-pathway alone, for nonproportioned shocks to A and B, and for shocks that proportioned 80% of the current to the B-pathway using either HF, sequential, or amplitude proportioning methods. All proportioning methods had similar I50s that were significantly lower than the I50 for nonproportioned shocks to A and B and that were comparable to shocks to the B-pathway alone. CONCLUSIONS: Shocks with most current proportioned to the B-pathway had lower defibrillation currents than nonproportioned shocks using both pathways. Thus, defibrillation efficacy was changed by HF proportioning without changing the electrodes or shock waveform. These findings suggest that HF proportioning may be a method to improve defibrillation.

Animals↗

PubMed1975

Function of the classical and alternate pathways of human complement in serum treated with ethylene glycol tetraacetic acid and MgCl2-ethylene glycol tetraacetic acid.

An immunochemical and functional analysis of the classical and alternate complement pathways in human serum was performed in the presence of 10 mM ethylene glycol tetraacetic acid (EGTA) and MgCl(2)-EGTA (MgEGTA), chelating agents which have been recently utilized as a means of distinguishing between these two complement pathways. Total hemolytic activity, integrity of the C1 complex, hemolytic activity of C2, conversion of factor B (C3 proactivator), and complement-dependent bactericidal activity were studied. The effect of these chelators on activation of complement pathways by Escherichia coli, by sensitized erythrocytes as a prototype of activators of the classical pathway, and by zymosan as a prototype of alternate (properdin) pathway activators was studied. Human serum containing 10 mM EGTA, which provides almost no ionized calcium and considerably less ionized magnesium than unchelated serum, allowed consumption of complement via the alternate (properdin) pathway, but blocked the classical pathway as judged by disintegration of the C1 complex and lack of utilization of C2. However, activity of the alternate complement pathway in EGTA serum, as judged by conversion of factor B and bactericidal activity against gram-negative bacteria, was distinctly suboptimal. Addition of magnesium ion in a concentration equimolar to EGTA (MgEGTA serum), while still providing conditions in which the C1 complex dissociated, significantly enhanced alternate complement pathway-mediated bactericidal activity. However, in MgEGTA serum considerable fluid-phase activation of the alternate pathway, as indicated by decrease in 50% hemolytic complement (CH(5 0)) titers and conversion of factor B to its active form in the absence of any activating challenge, was observed. Moreover, some fluid-phase consumption of C2 was observed in MgEGTA serum, even though, as mentioned, the C1 complex was shown to be dissociated under these conditions. MgEGTA-related activation of C2 and of the alternate (properdin) pathway of complement was significantly enhanced by the presence of zymosan and E. coli. These results indicate that use of the chelating agents EGTA and MgEGTA to differentiate between classical and alternate pathway activation of human complement is more complex than has hitherto been suggested. In EGTA serum, spontaneous activation of either pathway does not occur but bactericidal activity, as a measure of biologic function of complement, is suboptimal. In MgEGTA serum, bactericidal activity is fully expressed, but there is considerable instability, in terms of fluid-phase activation, in Mg(2+)-dependent components of both pathways. Thus, caution is indicated in the use and interpretation of the effects of these chelating agents on biologic functions mediated by either pathway of human complement.

Blood Bactericidal Activity↗

PubMed1992

Selective radiofrequency ablation of the slow pathway for the treatment of atrioventricular nodal reentrant tachycardia. Evidence for involvement of perinodal myocardium within the reentrant circuit.

BACKGROUND: The circuit of atrioventricular (AV) nodal reentrant tachycardia may include perinodal atrial myocardium. Furthermore, in patients with dual AV nodal pathways, the atrial insertion of the slow pathway is likely to be located near the ostium of the coronary sinus, caudal to the expected location of the AV node. The present study was designed to evaluate the safety and efficacy of selective catheter ablation of the slow pathway using radiofrequency energy applied along the tricuspid annulus near the coronary sinus ostium as definitive therapy for AV nodal reentrant tachycardia. METHODS AND RESULTS: Among 34 consecutive patients who were prospectively enrolled in the study, the slow pathway was selectively ablated in 30, and the fast pathway was ablated in four. Antegrade conduction over the fast pathway remained intact in all 30 patients after successful selective slow pathway ablation. There was no statistically significant change in the atrio-His interval (68.5 +/- 21.8 msec before and 69.6 +/- 23.9 msec after ablation) or AV Wenckebach rate (167 +/- 27 beats per minute before and 178 +/- 50 beats per minute after ablation) after selective ablation of the slow pathway. However, the antegrade effective refractory period of the fast pathway decreased from 348 +/- 94 msec before ablation to 309 +/- 79 msec after selective slow pathway ablation (p = 0.005). Retrograde conduction remained intact in 26 of 30 patients after selective ablation of the slow pathway. The retrograde refractory period of the ventriculo-atrial conduction system was 285 +/- 55 msec before and 280 +/- 52 msec after slow pathway ablation in patients with intact retrograde conduction (p = NS). There were three complications in two patients, including an episode of pulmonary edema and the development of spontaneous AV Wenckebach block during sleep in one patient after slow pathway ablation and the late development of complete AV block in another patient after fast pathway ablation. Over a mean follow-up period of 322 +/- 73 days, AV nodal reentrant tachycardia recurred in three patients, all of whom were successfully treated in a second ablation session. CONCLUSIONS: Radiofrequency ablation of the slow AV pathway is highly effective and is associated with a low rate of complications.

Adult↗

PubMed1995

Effect of dual atrioventricular node pathways on atrioventricular reentrant tachycardia.

BACKGROUND: Dual atrioventricular (AV) node pathway physiology is frequently observed in patients with AV accessory pathways. METHODS AND RESULTS: To examine the implications of this, we identified 36 patients (19 men and 17 women; mean +/- SD age, 30 +/- 13 years) with both phenomena. The 36 patients had 48 accessory pathways. Twenty-seven patients had bidirectional and 9 had unidirectional accessory pathways. Of the 34 patients with inducible atrioventricular reentry, 17 used the slow and 11 used the fast anterograde AV node pathway exclusively during AV reentrant tachycardia, whereas 6 patients used both the fast and the slow AV node pathways. AV node reentrant tachycardia was inducible in addition to AV reentry in 7 patients. Both the cycle length and AH intervals were significantly longer during slow pathway-dependent (cycle length, 411 +/- 58 milliseconds [ms]; AH, 229 +/- 42 ms) than during fast pathway-dependent (cycle length, 322 +/- 40 ms; AH, 121 +/- 25 ms; P < .05) reentrant tachycardias. Two patients had only AV node reentrant tachycardia inducible despite the presence of the accessory pathway. Four patients with technically difficult accessory pathways were managed by AV node modification with slow pathway (3) or fast pathway (1) ablation. Three of them remained free of symptoms 7, 14, and 25 months after the procedure whereas 1 patient had recurrence of arrhythmia. CONCLUSIONS: AV reentrance with dual AV node pathways frequently depends exclusively on either the slow or the fast AV node pathway for clinical tachycardia. This may provide additional options for ablation in technically difficult cases when the accessory pathway is not otherwise problematic.

Adolescent↗

PubMed2003

PathMAPA: a tool for displaying gene expression and performing statistical tests on metabolic pathways at multiple levels for Arabidopsis.

BACKGROUND: To date, many genomic and pathway-related tools and databases have been developed to analyze microarray data. In published web-based applications to date, however, complex pathways have been displayed with static image files that may not be up-to-date or are time-consuming to rebuild. In addition, gene expression analyses focus on individual probes and genes with little or no consideration of pathways. These approaches reveal little information about pathways that are key to a full understanding of the building blocks of biological systems. Therefore, there is a need to provide useful tools that can generate pathways without manually building images and allow gene expression data to be integrated and analyzed at pathway levels for such experimental organisms as Arabidopsis. RESULTS: We have developed PathMAPA, a web-based application written in Java that can be easily accessed over the Internet. An Oracle database is used to store, query, and manipulate the large amounts of data that are involved. PathMAPA allows its users to (i) upload and populate microarray data into a database; (ii) integrate gene expression with enzymes of the pathways; (iii) generate pathway diagrams without building image files manually; (iv) visualize gene expressions for each pathway at enzyme, locus, and probe levels; and (v) perform statistical tests at pathway, enzyme and gene levels. PathMAPA can be used to examine Arabidopsis thaliana gene expression patterns associated with metabolic pathways. CONCLUSION: PathMAPA provides two unique features for the gene expression analysis of Arabidopsis thaliana: (i) automatic generation of pathways associated with gene expression and (ii) statistical tests at pathway level. The first feature allows for the periodical updating of genomic data for pathways, while the second feature can provide insight into how treatments affect relevant pathways for the selected experiment(s).

Arabidopsis↗

PubMed2004

A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases.

BACKGROUND: The PathoLogic program constructs Pathway/Genome databases by using a genome's annotation to predict the set of metabolic pathways present in an organism. PathoLogic determines the set of reactions composing those pathways from the enzymes annotated in the organism's genome. Most annotation efforts fail to assign function to 40-60% of sequences. In addition, large numbers of sequences may have non-specific annotations (e.g., thiolase family protein). Pathway holes occur when a genome appears to lack the enzymes needed to catalyze reactions in a pathway. If a protein has not been assigned a specific function during the annotation process, any reaction catalyzed by that protein will appear as a missing enzyme or pathway hole in a Pathway/Genome database. RESULTS: We have developed a method that efficiently combines homology and pathway-based evidence to identify candidates for filling pathway holes in Pathway/Genome databases. Our program not only identifies potential candidate sequences for pathway holes, but combines data from multiple, heterogeneous sources to assess the likelihood that a candidate has the required function. Our algorithm emulates the manual sequence annotation process, considering not only evidence from homology searches, but also considering evidence from genomic context (i.e., is the gene part of an operon?) and functional context (e.g., are there functionally-related genes nearby in the genome?) to determine the posterior belief that a candidate has the required function. The method can be applied across an entire metabolic pathway network and is generally applicable to any pathway database. The program uses a set of sequences encoding the required activity in other genomes to identify candidate proteins in the genome of interest, and then evaluates each candidate by using a simple Bayes classifier to determine the probability that the candidate has the desired function. We achieved 71% precision at a probability threshold of 0.9 during cross-validation using known reactions in computationally-predicted pathway databases. After applying our method to 513 pathway holes in 333 pathways from three Pathway/Genome databases, we increased the number of complete pathways by 42%. We made putative assignments to 46% of the holes, including annotation of 17 sequences of previously unknown function. CONCLUSIONS: Our pathway hole filler can be used not only to increase the utility of Pathway/Genome databases to both experimental and computational researchers, but also to improve predictions of protein function.

Amino Acid Oxidoreductases↗

PubMed2006

QPath: a method for querying pathways in a protein-protein interaction network.

BACKGROUND: Sequence comparison is one of the most prominent tools in biological research, and is instrumental in studying gene function and evolution. The rapid development of high-throughput technologies for measuring protein interactions calls for extending this fundamental operation to the level of pathways in protein networks. RESULTS: We present a comprehensive framework for protein network searches using pathway queries. Given a linear query pathway and a network of interest, our algorithm, QPath, efficiently searches the network for homologous pathways, allowing both insertions and deletions of proteins in the identified pathways. Matched pathways are automatically scored according to their variation from the query pathway in terms of the protein insertions and deletions they employ, the sequence similarity of their constituent proteins to the query proteins, and the reliability of their constituent interactions. We applied QPath to systematically infer protein pathways in fly using an extensive collection of 271 putative pathways from yeast. QPath identified 69 conserved pathways whose members were both functionally enriched and coherently expressed. The resulting pathways tended to preserve the function of the original query pathways, allowing us to derive a first annotated map of conserved protein pathways in fly. CONCLUSION: Pathway homology searches using QPath provide a powerful approach for identifying biologically significant pathways and inferring their function. The growing amounts of protein interactions in public databases underscore the importance of our network querying framework for mining protein network data.

Algorithms↗

PubMed1983

[Reciprocating tachycardia and anterograde conduction by a nodoventricular pathway].

Two patients were investigated for paroxysmal regular tachycardia with left bundle branch block centrifugation. A right-sided nodo-ventricular accessory pathway was demonstrated in both cases at electrophysiological investigation with His bundle recording and atrial and ventricular programd pacing techniques. However, the function of this pathway was different in the two cases. In the first case, there were no signs of an accessory pathway on the surface ECG in sinus rhythm but it could be unmasked by simple right atrial pacing at the same rhythm (widening of the QRS and shortening of HV from 40 to 25 ms). The tachycardias could be only initiated by ventricular extrastimulus. They showed major pre-excitation with left sided delay and a 1/1 atrio-ventricular response. There was no His potential before the ventriculogramme which retained the same configuration throughout the attack. The investigations also suggested the presence of a dual nodal pathway with the accessory pathway connected to the slow pathway. In the second case, the presence of an accessory pathway could be suspected from the appearance of the QRS complex in sinus rhythms. Tachycardia was initiated by an atrial extrastimulus with initially a first complex showing slightly more marked pre-excitation and a distinct His potential before the QRS but with a shorter HV interval than in sinus rhythm. Then the reciprocating tachycardia had appearances of major pre-excitation, left-sided delay and a 1/1 atrio-ventricular response. However, in contrast to the first case, all ventricular complexes were preceded by a His potential and the degree of pre-excitation was variable with a HV interval ranging from 0 to 15 ms. These two cases merit attention because of: --their points in common: nodal duality and an accessory pathway which was not atrio-ventricular (decremental conduction) but nodo-right ventricular, conducting well in the anterograde direction but more or less masked in sinus rhythm; the presence of the accessory pathway was clearly visible during reciprocating tachycardia; --the differences: in the first case the nodo-ventricular pathway formed part of the circuit of the reciprocating tachycardia which was antidromic: descending limb, the slow nodal pathway and then the accessory nodo-ventricular pathway; ascending limb, the His bundle and then the rapid nodal pathway. In the second case, the reciprocating tachycardia was entirely intranodal, the accessory pathway not being involved in the circuit but connected to it in parallel with the normal Hisian pathway.

Adult↗

PubMedDate not supplied

Characterization of two second messenger pathways and their interactions in eliciting the human sperm acrosome reaction.

The human sperm acrosome reaction (AR) occurs via the activation of at least two signal transduction pathways. The purpose of this investigation was to characterize two of the pathways, the protein kinase A (PKA) and C (PKC) pathways, and determine whether pathway "crosstalk" occurs between them in eliciting the AR in capacitated spermatozoa. Stimulators of each pathway were tested in a dose-dependent manner. ARmax, ED50, and delta ARmax (%ARmax-%ARcontrol) values were calculated. The PKA pathway stimulators forskolin and dibutyryl cyclic AMP (dbcAMP) induced an ARmax at 1.0 microM and 1.0 mM, respectively. The ED50 and delta ARmax values were: 0.01 microM and 17% for forskolin and 0.069 mM and 13% for dbcAMP. Two stimulator types of the PKC pathway were tested: synthetic diacylglycerols (DG) and a phorbol diester. 1,2-dioleoyl-sn-glycerol and 1,2-dioctanoyl-sn-glycerol, analogues of the PKC-activating second messenger DG, each induced an ARmax at 50 microM. The ED50 and delta AR max values were: 33 microM and 24% for 1,2-dioleoyl and 34.8 microM and 34% for 1,2-dioctanoyl. 4 beta-Phorbol-12,13-didecanoate, a PKC stimulator, induced an ARmax at 0.1 microM. The ED50 and delta ARmax were 0.021 microM and 26%. An inhibitor of each kinase was added at the end of the capacitation period and prior to stimulation by inducers at their ARmax dose. KT5720, a PKA inhibitor, caused a dose-dependent reduction of the forskolin and dbcAMP-induced AR. Calphostin C, a PKC inhibitor, prevented stimulation of the AR by 1,2-dioleoyl and 4 beta-phorbol-12,13-didecanoate. To investigate pathway "crosstalk," the following experiments were conducted: (1) stimulators of each pathway were combined and tested at the ARmax and ED50 concentrations for each; (2) spermatozoa were pretreated with a kinase inhibitor and then stimulated using an alternative pathway stimulator; and (3) a PKA or PKC inhibitor and a combination of PKA and PKC stimulators, at ED50 concentrations, were tested. The results for (1) indicate an additive AR response of ED50 concentrations but not for ARmax doses. The results for (2) demonstrate that a kinase inhibitor for one pathway prevents induction of the AR by a stimulator of the alternative pathway. Finally, the results for (3) show that a kinase inhibitor for one pathway prevents induction of the AR by the combined use of separate pathway stimulators. When taken collectively, the present results suggest a convergent mechanism of crosstalk between the PKA and PKC pathways leading to the human sperm AR.

Acrosome↗

PubMed2002

Design and impact of intraoperative pathways for head and neck resection and reconstruction.

OBJECTIVES: To describe the design and impact of 3 intraoperative pathways for the treatment of head and neck cancers; to detail the pathways schematically to illustrate projected intraoperative flow and teamwork; and to analyze impact on procedure and case lengths in each pathway and in comparison with historical prepathway average times. SETTING: Tertiary-level academic health system main operating room. PATIENTS: Twenty-one patients undergoing transcervical (TC) resection (n = 11), transmandibular (TM) resection (n = 8), or laryngopharyngectomy (LP) (n = 2) with radial forearm free-flap reconstruction for ablative or reconstructive reasons were pathway eligible. A convenience sample of 16 patients undergoing TC resection, 7 undergoing TM resection, and 7 undergoing LP prepathway is used for comparison. INTERVENTION: Our academic medical center uses 3 intraoperative clinical pathways to manage resource use and streamline care for patients. These 3 pathways were designed schematically by an interdisciplinary team. The pathways plan progression of the case by timed actions for surgical, anesthesia, and nursing teams. MAIN OUTCOME MEASURES: Procedure and case lengths. RESULTS: The TC pathway procedure and case length averaged 10.48 and 12.33 hours, respectively; TM pathway procedure and case lengths, 11.19 and 13.32 hours, respectively; and LP pathway procedure and case lengths, 12.42 and 13.83 hours, respectively. Aggregate averages were 10.93 hours and 12.85 hours for procedure and case length, respectively. The average pathway case lengths of 12.33, 13.32, and 13.83 hours compare favorably with our target times of 13, 14, and 15 hours, respectively. Environmental management, work flow, and team satisfaction anecdotally increased postpathway. CONCLUSIONS: Intraoperative pathways afford enhanced time and action efficiency to streamline care of patients undergoing head and neck procedures. Pathway implementation produced time savings. Our results suggest that implementation of such pathways will benefit similar academic medical centers seeking to improve intraoperative resource use to improve performance in the care of patients undergoing head and neck procedures.

Cervical Vertebrae↗

PubMed1998

Neuroplasticity in the cat's visual system. Origin, termination, expansion, and increased coupling of the retino-geniculo-middle suprasylvian visual pathway following early ablations of areas 17 and 18.

We used anterograde and retrograde transsynaptic pathway tracing techniques to reveal the retinal origin and the cortical termination of the expanded retino-geniculo-middle suprasylvian (MS) cortex pathway in adult cats which sustained lesions of areas 17 and 18 on the day of birth (P1) or at 1 month of age (P28). Following anterograde transsynaptic transport of tritiated amino acids from the eye, four major results were obtained: (1) a strong and specific pathway from retina through dorsal lateral geniculate nucleus (dLGN) to the posterior half of MS cortex was identified; this pathway is a substantial expansion of an insignificant pathway present in intact cats; (2) the terminus of the pathway was lower layer III and layer IV; (3) contralateral projections were stronger than ipsilateral projections; (4) projections in P28 cats were stronger than those in P1 cats. Following retrograde transsynaptic transport of WGA-HRP from posterior MS cortex, four additional results were obtained: (1) the pathway was enlarged and visuotopically organized; (2) the pathway arose primarily from alpha- and gamma-retinal ganglion cells; (3) a small number of beta-cells in P1 cats and a modest number in P28 cats also contribute to the pathway; (4) the combined numbers of gamma- and beta-cells relative to alpha-cells was greater in temporal retina than in nasal retina. The combined demonstration of both origin and terminus of the pathway with transsynaptic tracers argued strongly for high levels of coupling between primary and secondary pathway limbs in both P1 and P28 cats. This level of coupling, as well as other features of the pathway, have much in common with the retino-geniculo-17/18 pathway of intact cats. However, the retino-geniculo-MS system in P1 cats transmits primarily Y and W signals, in P28 cats X, Y, and W signals; whereas the retino-geniculo-17/18 pathway transmits primarily X and Y signals. These results have implications for understanding the repercussions of early visual cortex lesions in monkeys and humans.

Amino Acids↗

PubMed1992

Differences in aging in two neural pathways: proposed explanations from the nervous system of Aplysia.

A basic question in studies of the neurobiology of aging is to what extent age-related changes are genetically preprogrammed or epigenetically mediated. Our approach to this question is to compare the effect of age on two neural pathways in the marine mollusc, Aplysia. The advantage of Aplysia as a model of neural aging is that age-sensitive properties in the pathways can be studied at the behavioral, physiological, and morphological levels. The two pathways we are investigating respond differently to aging; a comparison of the pathways' properties provides a means of distinguishing the effect of age from other variables in the same animal. Age effects are expressed in the gill withdrawal reflex pathway at the three levels but are minimal in the gill respiratory pathway. The behavioral and physiological expressions of the reflex pathway are weakened in old animals (250 days of age and older) when compared to those in mature ones (ca. 160 days of age). The major differences between the two pathways are: (1) the reflex pathway appears to exhibit more plasticity than the respiratory pathway, and (2) the level of use of the respiratory pathway is more regular and frequent than that of the reflex pathway. The greater plasticity intrinsic to the reflex pathway and its level of use may well be the characteristics upon which age-related changes depend. An interplay between genetic and epigenetic factors is suggested to help explain the differential aging in the two pathways.

Aging↗

PubMed1997

The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry.

The current view of basal ganglia organization holds that functionally corresponding subregions of the frontal cortex, basal ganglia and thalamus form several parallel segregated basal ganglia-thalamocortical circuits. In addition, this view states that striatal output reaches the basal ganglia output nuclei (the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus (GPi)) via a 'direct' pathway, and via an 'indirect pathway' which traverses the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). However, the topographical relationships of GPe and STN, and their topographical relationships with the basal ganglia-thalamocortical circuits are still unclear. The present work reviewed primate data on the topographical organization of STN afferents from GPe, and STN efferents to the pallidum, striatum and SNR, and examined these data with respect to a tripartite (motor, associative and limbic) functional subdivision of the striatum and pallidum. This examination indicated the following. (1) On the basis of its efferent connections, the STN may be divided into a motor and an associative territories, as well as a smaller limbic territory, each projecting to corresponding areas in the pallidum and striatum. (2) Efferents from GPe are in a position to contact subthalamic cells projecting to GPi/SNR, thus providing anatomical support for the existence of indirect pathways. (3) Moreover, given the tripartite division of the striatum, pallidum, and STN, the available data indicate the existence of indirect pathways connecting functionally corresponding subregions of the striatum, pallidum, and STN, as well as indirect pathways connecting functionally non-corresponding subregions. On the basis of the above we suggested that there may be two types of indirect pathways, one which terminates in the same subregion in GPi/SNR as the direct pathway arising from the same striatal subregion, and another which terminates in a different GPi/SNR subregion than the direct pathway arising from the same striatal subregion. We termed the former a 'closed indirect pathway' and the latter an 'open indirect pathway'. The application of these concepts to the surveyed data suggested the existence of three closed indirect pathways, each connecting the corresponding functional (motor, associative, and limbic) regions of the striatum, pallidum, STN, and SNR, as well as of two open indirect pathways, one connecting the associative striatum to the motor subregions of the basal ganglia, and the other connecting the associative striatum to the limbic subregions of the basal ganglia. While the organization of the closed indirect pathways fits the closed segregated arrangement of basal ganglia-thalamocortical circuitry, the organization of the open indirect pathways fits the recently suggested open interconnected scheme of basal ganglia thalamocortical circuitry. The clinical implications of this scheme for Huntington's disease are discussed.

Animals↗

PubMed1997

Care pathway reduces hospitalizations and cost for hemodialysis vascular access surgery.

Hemodialysis vascular access-related hospitalizations account for more than 20% of United States end-stage renal disease (ESRD) hospitalizations, with an annual cost approximating $675 million. Limiting access-related costs while delivering similar degrees of quality care thus would enhance alternative utilization of ESRD funding. We implemented a vascular access care pathway emphasizing coordinated patient evaluation and outpatient surgery to determine whether such an intervention affected outcomes associated with vascular access surgery. Data examining hospitalization and vascular access surgery charges, complications, and patient satisfaction (determined by questionnaire) were analyzed, comparing patients who underwent vascular access surgery in 1994 and 1995 as inpatients (non-care pathway patients) and patients who underwent vascular access surgery via the care pathway in 1995. Inpatient days declined in 1995 (1994: 582 days; 1995: 85 days; P < 0.03) and the average charges per patient for the care pathway cohort were significantly less than charges per patient in 1994 and charges for non-care pathway patients in 1995 (1994 patients: $10,524 +/- $5,209; 1995 non-care pathway patients: $11,196 +/- $5,806; 1995 care pathway patients: $4,686 +/- $2,912/patient; P < 0.02). Incidence rates for major (life-threatening) complications were not significantly different between 1994 patients and care pathway patients in 1995. However, the 1995 non-care pathway patients had a higher incidence of major complications (15.4%). Forty-seven repeat access procedures were performed in 29 patients in 1994 versus 35 repeat access procedures in 22 care pathway patients in 1995, and 12 repeat access procedures were performed in eight non-care pathway patients in 1995. Finally, a majority of the patients entered into the care pathway who responded to a survey stated that they were satisfied with access surgery via the care pathway. These data suggest that a vascular access care pathway can reduce hospital days and costs while achieving acceptable outcomes for access surgery.

Ambulatory Surgical Procedures↗

PubMed2003

Does a clinical pathway improve the quality of care for sickle cell anemia?

BACKGROUND: Clinical pathways are often implemented to improve care, yet their effect on quality of care and outcomes is often not evaluated. The Johns Hopkins Children's Center instituted a clinical pathway in early 1996 to improve the care for pediatric sickle cell vaso-occlusive crisis (VOC) and used a retrospective before-after study to describe how quality of care and outcomes changed after introduction of the pathway. RESULTS: Physicians used the pathway in 43% of eligible admissions, with use decreasing over time. Patients on the pathway were more likely to receive each of its required elements than those not on the pathway (odds ratios [OR] 1.15-2.49). After pathway implementation, even patients not on the pathway were more likely to receive incentive spirometry than those admitted before pathway availability (OR 1.40). Pathway use was associated with longer length of stay (LOS) and time to oral pain medication, while readmission rates did not change. DISCUSSION: Use of a clinical pathway improved quality of care by increasing compliance with specific care elements, with mixed results on outcomes. Pathways may improve care for all patients, including nonpathway-treated patients, by influencing underlying practice patterns. Quality improvement committees must regularly monitor outcomes after pathway implementation to evaluate the need for pathway reinforcement and refinement.

Adolescent↗

PubMed1998

The effect of a perioperative clinical pathway for knee replacement surgery on hospital costs.

UNLABELLED: Clinical pathways are being introduced by hospitals to reduce costs and control unnecessary variation in care. We studied 766 inpatients to measure the impact of a perioperative clinical pathway for patients undergoing knee replacement surgery on hospital costs. One hundred twenty patients underwent knee replacement surgery before the development of a perioperative clinical pathway, and 63 patients underwent knee replacement surgery after pathway implementation. As control groups, we contemporaneously studied 332 patients undergoing radical prostatectomy (no clinical pathway in place for these patients) and 251 patients undergoing hip replacement surgery without a clinical pathway (no clinical pathway and same surgeons as patients having knee replacement surgery). Total hospitalization costs (not charges), excluding professional fees, were computed for all patients. Mean (+/-SD) hospital costs for knee replacement surgery decreased from $21,709 +/- $5985 to $17,618 +/- $3152 after implementation of the clinical pathway. The percent decrease in hospitalization costs was 1.56-fold greater (95% confidence interval 1.02-2.28) in the knee replacement patients than in the radical prostatectomy patients and 2.02-fold greater (95% confidence interval 1.13-5.22) than in the hip replacement patients. If patient outcomes (e.g., patient satisfaction) remain constant with clinical pathways, clinical pathways may be a useful tool for incremental improvements in the cost of perioperative care. IMPLICATIONS: Doctors and nurses can proactively organize and record the elements of hospital care results in a clinical pathway, also known as "care pathways" or "critical pathways." We found that implementing a clinical pathway for patients undergoing knee replacement surgery reduced the hospitalization costs of this surgery.

Adult↗

PubMed1999

Implementation of a clinical pathway decreases length of stay and cost for bowel resection.

OBJECTIVE: To examine the effect of a clinical pathway for small and large bowel resection on cost and length of hospital stay. SUMMARY BACKGROUND DATA: Clinical pathways are designed to streamline patient care delivery and maximize efficiency while minimizing cost. Theoretically, they should be most effective in commonly performed procedures, in which volume and familiarity are high. METHODS: A clinical pathway to assist in the management of patients undergoing bowel resection was developed by a multidisciplinary team and implemented. Data about length of stay and cost was collected for all patients undergoing bowel resection 1 year before and 1 year after pathway implementation. Three groups were compared: patients undergoing bowel resection in the year prior to pathway implementation (prepathway), patients in the year after pathway implementation but not included on the pathway (nonpathway), and patients included in the pathway (pathway). RESULTS: The mean cost per hospital stay was $19,997.35 +/- 1244.61 for patients in the prepathway group, $20,835.28 +/- 2286.26 for those in the nonpathway group, and $13,908.53 +/- 1113.01 for those in the pathway group (p < 0.05 vs. other groups). Mean postoperative length of stay was 9.98 +/- 0.62 days (prepathway), 9.68 +/- 0.88 days for (nonpathway), and 7.71 +/- 0.37 days (pathway) (p < 0.05 vs. other groups). CONCLUSIONS: Implementation of the pathway produced significant decreases in length of stay and cost in the pathway group as compared to the prepathway group. These results support the further development of clinical pathways for general surgical procedures.

Costs and Cost Analysis↗

PubMed1996

Synaptic connections between spiny neurons of the direct and indirect pathways in the neostriatum of the rat: evidence from dopamine receptor and neuropeptide immunostaining.

UNLABELLED: The flow of cortical information through the basal ganglia occurs through the so-called 'direct pathway' and 'indirect pathways'. The object of the present work was to attempt to determine whether spiny neurons in the neostriatum that give rise to the direct pathway (i.e. the striatonigral/entopeduncular pathway) and those giving rise to the indirect pathways (i.e. striatopallidal pathway) are synaptically interconnected. The approach was to carry out double immunocytochemistry at the electron microscopic level using antibodies against peptides or dopamine receptor subtypes that are selectively associated with the neurons that give rise to the direct (substance P or D1 receptors) and indirect pathways (enkephalin or D2 receptors). Sections of perfuse-fixed rat neostriatum were immunostained to reveal both substance P immunoreactivity and D2 receptor immunoreactivity or enkephalin and D1 receptor immunoreactivity, respectively. Double peroxidase methods were employed using different chromogens that were distinguishable at both the light and electron microscopic levels. In the electron microscope substance P-immunoreactive terminals were seen in synaptic contact with dendritic structures that displayed immunoreactivity for D2 receptor. Similarly, enkephalin-immunoreactive terminals were seen in synaptic contact with D1-immunoreactive dendritic structures. Thus, axon collaterals of neurons giving rise to the direct pathway form synaptic contacts with neurons that give rise to the indirect pathway and axon collaterals of neurons giving rise to the indirect pathway form synaptic contact with neurons that give rise to the direct pathway. These results indicate that the two pathways of information flow through the basal ganglia are synaptically linked at the level of the neostriatum. KEYWORDS: spiny neurons, direct pathway,indirect pathways, rat neostriatum

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