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PubMed1981

The respiration pathways of wild-type and petite mutants of Kluyveromyces lactis.

The existence of two alternative respiration pathways in Kluyveromyces lactis has been confirmed. Both pathways may be demonstrated in petite mutants of this yeast, suggesting that the major components in these pathways have an extramitochondrial origin. The antimycin A insensitive/sodium azide insensitive pathway (pathway I) is abolished by glucose repression of this yeast, whereas the antimycin A insensitive/sodium azide sensitive pathway (pathway II) is unaffected by this treatment. In K. lactis wild-type cells, the antimycin A insensitive/sodium azide sensitive respiration pathway (pathway II) is inhibited by salicyl hydroxamic acid, and this inhibition may be overcome upon addition of exogenous Fe3+ ions. This pathway in petite cells is unaffected by the presence of this inhibitor. The possible reasons for this are discussed.

Antimycin A↗
PubMed1994

[High frequency catheter ablation of left-sided manifest accessory conduction pathways during sinus rhythm and in continuous atrial fibrillation].

Atrial fibrillation is frequently initiated during radiofrequency catheter ablation of accessory pathways. It has been generally believed that initiation of atrial fibrillation may complicate the localization of accessory pathway. Therefore, most centers currently perform cardioversion in order to continue the ablation session. The purpose of the present study was to assess the feasibility and the electrophysiologic criteria for successful radiofrequency catheter ablation of left sided accessory pathways during atrial fibrillation in patients with WPW-syndrome. Radiofrequency ablation was performed in 87 patients with left-sided manifest accessory pathways during atrial fibrillation (n = 16) or during sinus rhythm (n = 71). The criteria for localization of accessory pathways were recording of stable accessory pathway potentials, local ventricular activation preceding the onset of the intrinsic flection of the unipolar electrogram and a QS pattern of the unipolar electrogram. Overall, the accessory pathways were successfully interrupted in 85/87 patients (98%). During the first ablation procedure, abolishing of accessory pathways was achieved in 15 of 16 patients (94%) during atrial fibrillation compared to 64 of 71 patients (90%) during sinus rhythm (n.s.). The total procedure time and fluoro time was significantly shorter during atrial fibrillation than during sinus rhythm (161 +/- 91 min vs. 216 +/- 128 min, p < 0.05, and 31 +/- 24 vs. 41 +/- 26 min. p < 0.05, respectively). Thus, it is feasible and very effective to perform radiofrequency ablation of left-sided manifest accessory pathways during atrial fibrillation. Precise localization of accessory pathway during atrial fibrillation seems even easier than during sinus rhythm as indicated by shorter procedure and fluoro times in the atrial fibrillation group.

Adolescent↗
PubMed1994

[Radiofrequency ablation of the slow nodal pathway in cases of paroxysmal nodal reentry tachycardia].

INTRODUCTION: We describe our experience in the treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of the slow pathway. PATIENTS AND METHODS: Thirty-four patients (mean age 52 +/- 13 years) with recurrent drug refractory atrioventricular nodal reentrant tachycardia underwent radiofrequency catheter ablation of slow-pathway as the first procedure. Maximal energy used was 28 +/- 8 W, mean time was 4.4 +/- 2.8 min, and a mean number of 13 +/- 9 discharges per patient. RESULTS: Of the 34 patients 14 were successfully treated (no slow-pathway conduction, no AV nodal reentrant echo complexes, no inducible tachycardia), 11 were considered as partially successful (no inducible tachycardia, with slow-pathway conduction or echoes) and 9 patients were unsuccessfully treated (all of them underwent fast-pathway ablation with a successful outcome). Eight recurrences were observed during a mean follow-up period of 7 +/- 4 months: One in a patient with previously successful ablation (remained asymptomatic while taking beta-blockers), 6 in patients with first procedure partially successful (all of them underwent effective second slow-pathway ablation) and 1 in a patient with an unsuccessful procedure that underwent fast pathway ablation. A repeated procedure was successful in ablating the slow pathway. None of our patients developed complete atrio-ventricular block. One patient developed cardiac tamponade that needed surgical drainage. At last follow-up all patients are free from tachycardias. CONCLUSION: Slow pathway ablation is an effective method of treatment in patients with atrio-ventricular nodal reentrant tachycardia. Long term success is related to complete abolition of slow pathway conduction.

Adolescent↗
PubMed1993

[The predictors of success in the radiofrequency ablation of left accessory pathways using the single-catheter technic].

INTRODUCTION AND OBJECTIVES: To determine the predictors of successful radiofrequency current ablation of an accessory pathway using the single-catheter approach, we retrospectively analyzed 46 consecutive patients with left sided accessory atrioventricular pathways and manifest preexcitation. METHODS: Ablation using a single catheter advanced retrogradely towards the mitral valve was successful in 42 (91%). A radiofrequency pulse resulting in permanent accessory pathway block was defined as a successful pulse; a pulse that had no effect or caused only transient accessory pathway block was defined as an unsuccessful pulse. RESULTS: Successful radiofrequency pulses (n = 37) did not differ from those that failed (n = 56) in the local atrium-accessory pathway potential interval, in the accessory pathway-ventricle interval nor in the cumulative energy delivered. But in successful radiofrequency pulses, the amplitude ratio of local atrium and ventricular potentials tended to be larger (0.29 +/- 0.17 vs 0.23 +/- 0.17; p = 0.053) and presumed accessory pathway potential was more often recorded (36 [97%] vs 38 [68%]; p = 0.006). The time elapsed from the beginning of the current application and the accessory pathway block was shorter in successful pulses as compared to those pulses producing only transient block (3.3 +/- 2 s vs 6.9 +/- 4 s). CONCLUSIONS: The recording of a presumed accessory pathway potential, a large local A/V ratio and the occurrence of early conduction block in the accessory pathway were the best predictors of successful radiofrequency current application using the single-catheter approach.

Adolescent↗
PubMedDate not supplied

[Radiofrequency ablation in multiple accessory pathways].

Radiofrequency ablation were performed in 465 consecutive patients with Wolff-Parkinson-White syndrome. We demonstrated evidence of multiple accessory pathways in 18 patients (3.9%); 17 had two, and one had three accessory pathways. In three of these there was additional right atrio-fascicular connection. There were 27 manifest and 10 concealed accessory pathways. Six patients had Ebstein's anomaly associated with accessory pathways. The location of the accessory pathways was in the right posterior portion of the ventricular septum in 16, the left posterior portion of the ventricular septum in 5, the right free wall in 5, the left wall in 7, the right anteroseptal in 3, the midseptum in 1, and one right anterolateral. Of the 37 pathways, 32 (86%) accessory pathways were ablated successfully without complications. Duration of the procedure was 100 +/- 58 minutes, and fluoroscopic time 40 +/- 17 minutes. The mean applications were 26 +/- 17 and the power level of the radiofrequency current 41 +/- 6 W. A follow-up of 80 +/- 40 days after ablation demonstrated incidence of recurrent conduction in 3 accessory pathways (8%). In conclusion, patients with multiple accessory pathways can be treated by radiofrequency ablation in a single session with a high success rate although slightly less than that in patients with a single accessory pathway.

Catheter Ablation↗
PubMed1998

Radiofrequency catheter ablation of atrio-ventricular accessory pathways.

Radiofrequency catheter ablation of accessory pathways may represent the treatment of choice for patients with symptomatic atrio-ventricular reentrant tachycardia or atrial fibrillation and a high ventricular response through the accessory pathways with short antegrade refractory period. Moreover, catheter ablation has contributed towards understanding anatomical and electrophysiological characteristics of accessory pathways. As far as anatomical characteristics accessory pathways may be classified into fibers with proximal insertion in right or left atrium and fibers with proximal insertion in the atrio-ventricular nodal junction. As far as electrophysiological properties are concerned, accessory pathways may be differentiated into non-decremental and decremental. In non-decremental by-pass tracts (the so-called Kent bundles) the impulse can be conducted antegradely, retrogradely and in both directions. Decremental accessory pathways generally show only antegrade conduction properties (the so-called Mahaim fibers) and can be classified in long and short pathways; in particular, catheter ablation has given considerable evidence that the vast majority (but not all) of them has a proximal insertion on the tricuspid anulus (atrio-ventricular pathways) or on the atrio-ventricular node (nodo-ventricular pathways). Decremental accessory pathways with only retrograde conduction properties are involved in the so called "Permanent Junctional Reciprocating Reentrant Tachycardia".

Atrial Fibrillation↗
PubMed1986

Role of ascending and descending noradrenergic pathways in the antinociceptive effect of baclofen and clonidine.

Baclofen and clonidine interact with central noradrenaline (NA) pathways by a variety of mechanisms. The specific role of ascending and descending pathways in antinociception produced by these agents was examined by lesioning the dorsal bundle (DB), locus coeruleus (LC) and descending NA pathways by the microinjection of the neurotoxin 6-hydroxydopamine (6-OHDA). Lesions were verified using high-performance liquid chromatography analysis of NA. Both baclofen and clonidine were injected intraperitoneally in all experiments. The antinociceptive effect of baclofen in the tail-flick test was inhibited 7-21 days after DB lesions. This manipulation decreased NA levels in cortex, hippocampus and hypothalamus but did not alter spinal cord levels. Lesions of the LC potentiated the effect of baclofen 12-16 days postlesion. NA levels were reduced in all the regions just mentioned. DB lesions produced a transient decrease in the effect of clonidine, being observed 7 but not 12-16 days postlesion. Neither acute depletion of NA levels with alpha-methyl-p-tyrosine (alpha-MPT), nor LC lesions significantly affected antinociception produced by clonidine. Intraspinal 6-OHDA potentiated the antinociceptive action of clonidine in the tail-flick test. This treatment markedly reduced spinal cord NA levels, but had minimal effects on brain NA. The results of this and previous studies in this laboratory suggest that the antinociceptive effect of baclofen is mediated by interactions with both ascending and descending NA pathways. These pathways appear to interact in a complex manner. Interpretation of data for clonidine is complicated because lesions can both deplete endogenous NA as well as inducing postsynaptic supersensitivity of alpha 2-receptors. Clonidine does not depend on endogenous NA pathways for producing antinociception because acute depletion of NA with alpha-MPT does not alter its action. Spinal sites of action are of importance following systemic clonidine because intraspinal 6-OHDA produces supersensitivity. Altering NA activity in ascending pathways alone produces a transient inhibition of the effect of clonidine, but supersensitivity is not apparent. Simultaneous lesions of both ascending and descending pathways do not produce supersensitivity, again suggesting important interactions between such pathways can occur.

Afferent Pathways↗
PubMed1985

Equine alternative pathway activation by unsensitized rabbit red blood cells.

The equine alternative complement pathway has been partially characterized and compared to the equine classical activation pathway. A dose-dependent lysis of RbRBC was observed with peak lytic values noted within 10 minutes at 37 degrees C when rabbit red blood cells (RbRBC) were used as an alternative pathway activator. Sheep red blood cells (SRBC) sensitized with rabbit hemolysin or partially purified equine IgM antibodies were equally sensitive to lysis. Dilution of the commercial hemolysin by 1/5 reduced lysis from 90% to 38% in the presence of constant cell numbers. Hemolysis of SRBC peaked at 10 minutes and the majority of lysis occurred within 10 minutes. Dilution of equine sera by as little as 1/5 decreased hemolytic activity for SRBC to 21.5% from greater than 90% with undiluted sera. The alternative pathway protein, equine factor B, was tested using RbRBC and monitored by its differential susceptibility to heat treatment at 50 degrees C. This treatment led to almost complete inactivation after a 15-minute incubation. An apparent heat-dependent decay of certain classical pathway components was also observed after 50 degrees C treatment. This sensitivity was indicated by a reduction in the lytic activity for sensitized SRBC. Treatment for 15 minutes at 56 degrees C with either RbRBC or SRBC was sufficient to abolish hemolytic activity in all equine sera tested. Chelation of cations with 0.04 M EDTA blocked expression of alternative and classical pathway activation; however, chelation of Ca++ ions with 10 mM EGTA containing 1 mM Mg++ ions permitted lysis of the RbRBC but not the SRBC. A dose-related Mg++-ion dependence for RbRBC hemolytic activity was observed as the concentration of Mg++ was increased to 1.0 mM. In addition, our results obtained with pre-colostral foal serum strongly suggest that natural antibody to RbRBC was of little importance in the lysis observed with these cells. These results also show that the equine alternative pathway activation may require Ca++ ions. If Ca++ ions are required, the equine alternative pathway is quite different from any other mammalian complement system so far described. Our results suggest that the alternative pathway of activation is of major importance in the equine complement system. Confirmation of this hypothesis requires both purification of the components involved as well as further characterization.

Animals↗
PubMed2000

Inhibition of complement alternative pathway function with anti-properdin monoclonal antibodies.

Complement activation products appear to contribute to the pathology of several acute and chronic inflammatory conditions. The relative contributions of the classical and alternative complement pathways to these pathologies have, in large part, been undefined. Considerable progress has been made recently in identifying inhibitors of complement activation and demonstrating that such molecules can attenuate inflammation in various models of disease. However, most of these complement inhibitors affect aspects of both the classical and alternative pathways. In an effort to better define the role of the alternative complement pathway in complement-mediated inflammatory conditions, we have developed monoclonal antibodies that specifically inhibit alternative pathway function. These blocking antibodies bind human properdin with high avidity and prevent its interaction with the alternative pathway C3 convertase. This results in a cessation of alternative pathway function in several in vitro assay systems. When tested in a model of cardiopulmonary bypass, in which human blood passes through tubing, a selected antiproperdin antibody caused nearly complete inhibition of the C3a and C5b-9 formation that was seen in untreated blood. Moreover, the anti-properdin agent resulted in a dramatic reduction of neutrophil and platelet activation in the bypass model. Surprisingly, the monoclonal antibody also caused a significant inhibition of C5b-9 generation when classical pathway activators, such as heparin-protamine or immune complexes, were added to human blood. These latter data suggest that the alternative pathway contributes significantly to the formation of complement activation products in blood when the classical pathway is initially triggered.

Antibodies, Monoclonal↗
PubMed1994

Differential behavioral effects of supracallosal and infracallosal lesions of the septohippocampal pathways: no ameliorative effects of oxotremorine or pilocarpine on radial-maze performance.

We examined the effects in young adult female Long-Evans rats of single or combined lesions of the infracallosal and supracallosal septohippocampal pathways on a battery of behavioral tasks over two postoperative periods (14-65 and 75-150 days, respectively). During the first period, rats with lesions of the infracallosal pathways, whether given alone or in combination with lesions of the supracallosal pathways, were more active in the open field and in their home cage, and showed increased reactivity to novel extracage stimuli. Behavioral results during the second postoperative period were similar to those of the first except that rats with lesions of the infracallosal pathways (either alone or in combination with lesions of the supracallosal pathways) were no longer hyperactive in their home cage and rats with the infracallosal lesion alone were no longer hyperactive in the open field. We also observed in rats with lesions of the infracallosal pathways impaired performance in the radial-arm maze task, whether conducted under an uninterrupted protocol (first and second postoperative periods) or with a 1-min intratrial interruption (second postoperative period). Thus, behavioral deficits were observed only in rats with a lesion to the infracallosal component of the septohippocampal pathways, the behavior of rats with the combined lesions being similar to that of rats with single lesions of the infracallosal pathways in most measures. The behavior of rats with lesions of the supracallosal pathways did not differ from that of sham-operated controls in any measure at either postoperative period. Acute, systemic injections of oxotremorine (0.03 or 0.1 mg/kg, ip) or pilocarpine (0.32 or 1.0 mg/kg, ip), two muscarinic agonists, did not affect radial-arm maze performance under either the uninterrupted or interrupted protocol. The use of nonspecific muscarinic agonists does not appear to be sufficient to enhance radial-arm maze performance in rats with infracallosal septohippocampal lesions which, in contrast to supracallosal lesions, were shown to induce a deficit in this task.

Afferent Pathways↗
PubMed2004

Immunoglobulin M-enriched intravenous immunoglobulin inhibits classical pathway complement activation, but not bactericidal activity of human serum.

Acute or even hyperacute humoral graft rejection, mediated by classical pathway complement activation, occurs in allo- and xenotransplantation due to preformed anti-graft antibodies. Intravenous immunoglobulin (IVIg) preparations can prevent complement-mediated tissue injury and delay hyperacute xenograft rejection. It is known that IgM-enriched IVIg (IVIgM) has a higher capacity to block complement than IVIgG. Different IVIgs were therefore tested for specificity of complement inhibition and effect on anti-bacterial activity of human serum. IVIgM-I (Pentaglobin), 12% IgM), IVIgM-II (IgM-fraction of IVIgM-I, 60% IgM), and three different IVIgG (all >95% IgG) were used. The known complement inhibitor dextran sulfate was used as control. Hemolytic assays were performed to analyze pathway-specificity of complement inhibition. Effects of IVIg on complement deposition on pig cells and Escherichia coli were assessed by flow cytometry and cytotoxicity as well as bactericidal assays. Complement inhibition by IVIgM was specific for the classical pathway, with IC50 values of 0.8 mg/ml for IVIgM-II and 1.7 mg/ml for IVIgM-I in the CH50 assay. Only minimal inhibition of the lectin pathway was seen with IVIgM-II (IC50 15.5 mg/ml); no alternative pathway inhibition was observed. IVIgG did not inhibit complement in any hemolytic assay. Classical pathway complement inhibition by IVIgM was confirmed in an in vitro xenotransplantation model with PK15 cells. In contrast, IVIgM did not inhibit (mainly alternative pathway mediated) killing of E. coli by human serum. In conclusion, IgM-enriched IVIg is a specific inhibitor of the classical complement pathway, leaving the alternative pathway intact, which is an important natural anti-bacterial defense, especially for immunosuppressed patients.

Animals↗
PubMed1999

Neurochemical gradients along monkey sensory cortical pathways: calbindin-immunoreactive pyramidal neurons in layers II and III.

We examined the distribution of neurons containing immunoreactivity for three calcium-binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally-directed somatosensory and auditory cortical pathways. Calbindin-immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally-directed somatosensory and auditory pathways. The number of calbindin-immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin-immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.

Animals↗
PubMed1987

Activation of the classical and alternative pathways of complement by Treponema pallidum subsp. pallidum and Treponema vincentii.

Both in vivo and in vitro studies have indicated that complement plays an important role in the syphilitic immune responses. Few quantitative data are available concerning activation of the classical pathway by Treponema pallidum subsp. pallidum, and no information is available on treponemal activation of the alternative pathway. Activation of both pathways was compared by using T. pallidum subsp. pallidum and the nonpathogen T. vincentii. With rabbit and human sources of complement, both organisms rapidly activated the classical pathway, as shown by hemolysis of sensitized sheep erythrocytes and by the generation of soluble C4a. With human sources of complement, both organisms also activated the alternative pathway, as shown by hemolysis of rabbit erythrocytes and by the generation of soluble C3a in the presence of magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). During incubation, organisms remained actively mobile and did not lyse, indicating that activation was a function of complement reactivity with the intact outer treponemal surface. In addition, freshly harvested T. pallidum subsp. pallidum immediately activated both pathways of complement; preincubation of organisms did not enhance complement reactivity. T. vincentii was a more potent activator of this pathway. T. pallidum subsp. pallidum contained almost four times as much surface sialic acid as T. vincentii did. When sialic acid was enzymatically removed from T. pallidum subsp. pallidum, enhanced activation of the alternative pathway was detected. It is proposed that T. pallidum subsp. pallidum retards complement-mediated damage by the alternative pathway through surface-associated sialic acid. This may be an important virulence determinant that enables these organisms to readily disseminate through the bloodstream to infect other tissues.

Animals↗
PubMed1996

Distinct characteristics of initiation of the classical and alternative complement pathways by Candida albicans.

Candida albicans is a potent activator of the complement system. The objective of this study was to characterize factors that influence the kinetics for activation of C3 and binding of C3 fragments to C. albicans. Factors that were examined included the surface properties of the yeast and contributions of the classical and alternative complement pathways. The results showed that incubation of hydrophobic, hydrophilic, or germinating yeast cells in normal human serum (NHS) containing radiolabeled C3 led to immediate accumulation of C3 on all three cell types, although the rate of accumulation of C3 on germinating cells was lower. An examination of the sites for early C3 binding showed that classical pathway initiation led to immediate, synchronous binding over the entire cell surface. A blockade of the classical pathway by absorption of putative classical pathway initiators or by chelation of calcium limited activation to the alternative pathway. Binding of C3 solely via the alternative pathway was characterized by a significant lag in the initial binding kinetics. In the absence of classical pathway initiation, the early cellular sites for C3 binding appeared as random, asynchronous foci of C3 that appeared to expand with time. The factor(s) mediating rapid deposition of C3 that was characteristic of the classical pathway initiation was reciprocally cross-absorbed by hydrophilic and hydrophobic C. albicans but was not removed by absorption of NHS with Saccharomyces cerevisiae, encapsulated Cryptococcus neoformans, or nonencapsulated C. neoformans. Delayed binding of C3 produced by absorption of serum was largely reversed by addition to the absorbed serum of immunoglobulin G isolated from NHS, indicating a significant role for a naturally occurring anti-C. albicans immunoglobulin C. in classical pathway initiation.

Antibodies, Fungal↗
PubMed1981

Importance of the integrity of the inter-heavy-chain disulphide bond of rabbit IgG in the activation of the alternative pathway of human complement by the F(ab')2 region of rabbit IgG antibody in immune aggregates.

Immune aggregates formed from either rabbit IgG antibody or F(ab')2 antibody, and antigen, caused exactly the same extent of incubated with human serum under conditions when incubated with human serum under conditions allowing only alternative pathway activation. These observations confirm that the F(ab')2 region of the antibody molecule can cause alternative pathway activation and that this activation is not affected by the presence of the Fc region of the molecule when only alternative pathway activation is permitted. Under conditions allowing activation of both the classical and alternative pathways, increased alternative pathway activation was obtained with IgG antibody aggregates compared to that obtained with F(ab')2 antibody aggregates. On reduction and alkylation of principally he inter-heavy-chain disulphide bond in the IgG antibody, prior to aggregate formation, it was found that no activation of the alternative pathway by IgG aggregates took place under conditions allowing only alternative pathway activation. Treatment of the IgG antibody with reducing agent alone, or alkylating reagent alone, followed by dialysis and aggregate formation, yielded aggregates which caused alternative pathway activation values close to those obtained for untreated IgG aggregates. These results indicate that the integrity of the inter-heavy-chain disulphide bond of rabbit IgG antibody in immune aggregates is necessary to allow the F(ab')2 region of the IgG molecule to activate the alternative pathway of human complement.

Animals↗
PubMed1999

Development and implementation of a clinical pathway for patients undergoing total laryngectomy: impact on cost and quality of care.

BACKGROUND: The current health care climate demands the provision of quality patient care in a cost-effective manner. Clinical pathways define the essential components of care that are provided to patients with a specific diagnosis to achieve a desired outcome within a predetermined period. Development and implementation of clinical pathways streamline the provision of quality care in the most cost-effective manner. OBJECTIVES: To develop a clinical pathway for patients undergoing total laryngectomy and to evaluate its impact on the cost and quality of care provided to these patients. SETTING: A tertiary care academic medical center. PATIENTS AND METHODS: A total of 45 patients were included in the study. The clinical pathway was implemented for 15 patients, while the other 30 patients were treated without the implementation of the pathway guidelines. MAIN OUTCOME MEASURES: Length of hospital stay, readmission rate, and hospital variable costs. RESULTS: The clinical pathway affected all cost outcome measures. Length of stay decreased by 2.4 days (29%; P=.001), and the average hospital variable cost decreased from $3992 to $3419 per case. This represents a 14.4% reduction in cost associated with pathway implementation (P=.02). The standardization of care eliminated unnecessary variation and repetition in resource usage, resulting in overall cost reduction. Pathway implementation resulted in a lower readmission rate (7% [1/15]) than that of patients treated prior to protocol implementation (23% [7/30]). CONCLUSION: Implementing a carefully developed clinical pathway may reduce cost without compromising the quality of care for patients undergoing total laryngectomy.

Cost Control↗
PubMed2001

Enteric pathways in the stomach.

This report summarises the characteristics of target specific projection and neurochemical coding patterns of motor and interneuronal pathways in the gastric enteric nervous system (ENS) which are involved in the innervation of the mucosa, the circular and the longitudinal muscle. The pathways were identified by retrograde tracing and further characterised by optical and intracellular recordings of the synaptic activation of muscle motor neurones, and by recordings of pathway-specific muscle responses. All motor pathways had polarised projections consisting of ascending cholinergic and descending nitrergic populations. Thus, both muscle layers were innervated by excitatory and inhibitory motor neurones. Their projections indicated the presence of intrinsic circuits that mediate excitatory and inhibitory components of a peristaltic reflex and/or are involved in reflex mediated changes in gastric tone. Although polarised projections were also identified for interneuronal pathways, a substantial proportion of descending interneurones was cholinergic. Interneurones and longitudinal muscle motor pathways had longitudinal projection preferences whereas circular muscle motor pathways had circumferential projection preferences. Target-specific coding was primarily revealed for cholinergic populations; ChAT/ENK/+/-SP neurones projected to the muscle layers, ChAT/NPY/+/-VIP projected to the mucosa and ChAT/+/-SP/+/-5-HT/+/-Calret/+/-Calb were interneurones. Muscle strip recordings revealed the functional significance of ascending excitatory and descending inhibitory pathways to the circular muscle and the prominent influence of ascending and descending cholinergic interneurones which activated excitatory and inhibitory circular muscle motor neurones through nicotinic synapses. It is concluded that enteric pathways in the stomach have region specific features which reflect structural and functional adaptation of the gastric ENS.

Animals↗
PubMed2002

In-hospital care pathways for stroke.

BACKGROUND: Care within a stroke unit reduces death or dependency after stroke. However, studies have found significant variations in clinical practice, access to stroke unit care, organisation of patient care, and clinical outcome. Stroke care pathways have been introduced as a method to promote organised and efficient patient care that is based on best evidence and guidelines. OBJECTIVES: We aimed to assess the effects of care pathways, as compared to standard medical care, among patients with acute stroke who had been admitted to hospital. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Trials Register (last searched in May 2001), the Cochrane Controlled Trials Register (Issue 4, 2000), MEDLINE (1975-2000), EMBASE (1980-2000), CINAHL (1982-2000), the Index to Scientific and Technical Proceedings (ISTP, May 2001), and HealthSTAR (May 2001). We also handsearched the Journal of Managed Care (1997 to 1998), which was later renamed the Journal of Integrated Care (1998 to 2001). Reference lists of articles were searched. SELECTION CRITERIA: We considered randomised controlled trials and non-randomised studies (quasi-randomised trials, comparative studies, controlled and uncontrolled before and after studies, and interrupted time series) that compared care pathway care with standard medical care. DATA COLLECTION AND ANALYSIS: One reviewer selected studies for inclusion and the other independently checked the decisions. Two reviewers independently assessed the methodological quality of the studies. One reviewer extracted the data and the other checked the extracted data. Data from randomised and non-randomised studies were analysed separately. We found significant statistical heterogeneity in the analysis of two outcomes (computed tomography brain scanning and duration of stay). MAIN RESULTS: There were three randomised controlled trials (total of 340 patients) and seven non-randomised studies (total of 1673 patients) that compared care pathway care with standard medical care. We found no difference between care pathway and control groups in terms of death, dependency, or discharge destination. Evidence from mainly non-randomised studies suggests that patients managed using a care pathway may be: a) less likely to suffer a urinary tract infection (OR 0.38, CI 0.18 to 0.79), b) less likely to be readmitted (OR 0.11, CI 0.03 to 0.39), and c) more likely to have a computed tomography brain scan (OR 3.66, CI 1.45 to 9.27) or carotid duplex study (OR 2.45, CI 1.3 to 4.61). Evidence from randomised trials suggests that patient satisfaction and quality of life may be significantly lower in the care pathway group (P=0.02 and P<0.005 respectively). REVIEWER'S CONCLUSIONS: The use of care pathways to manage stroke patients in hospital may be associated with both positive and negative effects on the process of care and clinical outcomes. Since most of the results have been derived from non-randomised studies, they are likely to be influenced by potential biases and confounding factors. There is currently insufficient supporting evidence to justify routine implementation of care pathways for acute stroke management or stroke rehabilitation.

Critical Pathways↗