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PubMed1989

Evidence for multiple lytic pathways used by cytotoxic T lymphocytes.

Previous data generated by ourselves and others questioned the role of degranulation as a mechanism to explain CTL-mediated cytotoxicity. In this report we examine this tissue in greater depth. CTL-mediated lysis was probed with three different inhibitors. 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene inhibits degranulation in a wide range of cell types, including CTL. EGTA, through chelation of Ca2+, also inhibits degranulation processes in CTL, and would inhibit other events or processes dependent on extracellular Ca2+. We also used prolonged exposure to PMA to exhaust PKC activity in CTL. Using these inhibitors, we have defined three pathways of lysis used by CTL. One pathway requires Ca2+, is PMA sensitive, but does not depend on degranulation. The second pathway is independent of Ca2+, is not PMA sensitive, and also does not depend on degranulation. All primary CTL and cloned CTL lyse most target cells via pathway I. However, when confronted with certain target cells (which we have referred to previously as Ca2+-independent target cells), pathway II is induced. When pathway II is induced, pathway I apparently shuts down. We show here that pathway II does not depend on protein synthesis, and that it also leads to DNA solubilization in target cells. A limited number of cloned CTL use pathways I and II as just described, but use in addition, and simultaneously, a third pathway that appears to involve degranulation. This pathway is seen irregularly in most CTL clones, and may be influenced by levels of IL-2 in the culture medium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1986

Pathways for the reduction of oxidized glutathione in the Plasmodium falciparum-infected erythrocyte: can parasite enzymes replace host red cell glucose-6-phosphate dehydrogenase?

Plasmodium falciparum-infected human red cells possess at least two pathways for the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH): (1) the glucose-6-phosphate dehydrogenase (G6PD) pathway and (2) the glutamate dehydrogenase (GD) pathway using glutamate as a substrate. Uninfected erythrocytes lack the GD pathway. The NADPH generated can be used to reduce oxidized glutathione (GSSG), which accumulates in the presence of an oxidative stress. In red cell G6PD deficiency, this pathway is reduced or absent, and the host cells as well as the parasites within them are vulnerable to oxidant stress. In view of the presence of the GD pathway in parasitized red cells and the recent description of a parasite-derived G6PD enzyme, we have asked whether the pathways for the reduction of GSSG provided by the parasite can substitute for the host G6PD in red cells deficient in G6PD activity. We have devised a functional assay in which the reduction rate of GSSG is monitored in the presence of buffered infected or control red cell lysates and substrates. Infected G6PD-deficient erythrocytes were obtained from in vitro cultures after a single prior growth cycle of the parasites in G6PD deficient cells to eliminate contaminating normal red cells. The results show that only parasitized red cells can reduce GSSG via the GD pathway. In parasitized G6PD Mediterranean red cells (completely G6PD-deficient), there is a detectable GSSG reduction via the G6PD pathway, not found in uninfected lysates from the same individual. In G6PD A- (African type, featuring partial deficiency), a small increment in the G6PD-dependent reduction of GSSG can also be detected. However, when compared to G6PD normal red cells, the activities from the parasite-derived pathways are small and could not be considered substitutes for normal host enzyme activity. It is concluded that while the plasmodium provides additional pathways for the generation of NADPH that may serve its own metabolic needs, the host red cells and hence the parasite itself remain vulnerable to oxidant stress.

Erythrocytes↗
PubMed1996

[Lausanne experience in radiofrequency percutaneous ablation of the slow pathway in nodal tachycardia].

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most frequent paroxysmal supraventricular tachycardia and results from reentry in the atrioventricular nodal region via slow and fast pathways. The curative treatment of choice consists of selective radio-frequency catheter ablation of the slow pathway. In this retrospective study we report our experience of 73 consecutive patients suffering from AVNRT treated by selective slow pathway ablation and also review some features of AVNRT. AVNRT appeared for the first time at the age of 29 +/- 15 years and lasted for 17 +/- 13 years. In 37% of the patients AVNRT recurred at least weekly, 10% presented with syncope and 15% were admitted to hospital more than 5 times. On average, 2.5+/-1.6 drugs were prescribed to 66 of the 73 patients and 83% of them were drug-refractory. Selective slow pathway ablation was successfully performed in 65 patients (89%). The procedure, although effective, was complicated by atrioventricular block in 2 patients (2.7%) and failed in 6 patients. In 5 of them, fast pathway ablation was attempted and was successful in 2 cases, resulted in atrioventricular block in one case and failed in 2 cases. The complications, apart from atrioventricular block necessitating a pacemaker in all cases, were one pulmonary embolism and 2 pneumothorax. The mean follow-up for the 70 patients for whom ablation was effective (with or without atrioventricular block) is 12.7+/-7.3 months. AVNRT relapsed in 5 patients (7%); all of them underwent a second ablation with 4 successes (slow pathway) and one atrioventricular block (fast pathway after failed slow pathway ablation). 11 patients (16%) developed palpitations: in one case they were due to atrial fibrillation and in 10 cases they remained of unknown origin. The palpitations were of short duration and well tolerated, and these patients nevertheless felt an improvement after the ablation. Therefore, at medium term, 62 patients (85%) remained free from symptoms or only slightly symptomatic and without a pacemaker, and 51 of them (70%) remained completely asymptomatic and without a pacemaker. AVNRT can result in considerable morbidity and antiarrhythmic drugs are frequently ineffective. Slow pathway ablation is a safe and effective treatment for AVNRT. In our opinion, if AVNRT or medical treatment diminish the quality of life, ablation is indicated. When AVNRT presents with hemodynamic collapse, ablation is mandatory. Fast pathway ablation after failed slow pathway ablation is associated with a high incidence of atrioventricular block and is targeted only at very symptomatic patients who accept the possibility of definitive pacemaker implantation.

Adolescent↗
PubMedDate not supplied

Comparison of the activity of polyanions and polycations on the classical and alternative pathways of complement.

Polyanions and polycations inhibit activity of the alternative and classical pathways of complement. We compared polyanions (commercial porcine heparin, chondroitin sulfate A, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate C and heparatin sulfate) with polycations (salmon sperm protamine sulfate, poly-L-lysine, poly-L-arginine, polybrene and a synthetically prepared portion of platelet factor 4) for ability to inhibit alternative and classical pathway activity. The polyanions had considerably more activity on the alternative than on the classical pathway, whereas the polycations more profoundly inhibited classical than alternative pathway activity. For example, heparin, a polyanion, at 1.0 micrograms (7.7 x 10(-7) M based upon an Mr average of 13000)/10(7) cellular intermediates, inhibited alternative pathway activity and classical pathway activity by 77 and 14%, respectively, whereas protamine sulfate, a polycation, at 0.25 micrograms/10(7) cellular intermediates, inhibited these two pathways by 34 and 98%, respectively. These studies suggest that the capacity to inhibit complement activity is a common feature of highly charged substances and the polyanions preferentially inhibit the alternative pathway while polycations preferentially inhibit the classical pathway. In vivo these highly charged substances could play an important role in the tissues in regulating the activity of both pathways of complement.

Animals↗
PubMed1979

Requirements of immunoglobulin and the classical and alternative complement pathways for phagocytosis and intracellular killing of multiple strains of Gram-negative aerobic bacilli.

The requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing of clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Serratia marcescens by normal human polymorphonuclear leukocytes were determined. Human sera deficient in immunoglobulin or classical pathway activity, or both, were compared for their ability to promote phagocytosis os and killing of 13 bacterial strains by the polymorphonuclear leukocytes. Seven of the thirteen microorganisms required immunoglobulin for phagocytosis and killing and utilized only the classical complement pathway. Three required immunoglobulin and utilized both the classical and alternative pathways. The other three microorganisms required minimal immunoglobulin and utilized the alternative or classical pathway, or both. None of the microorganisms utilized the alternative pathway in immunoglobulin-deficient sera or could be forced to utilize this pathway in sera deficient in both immunoglobulin and classical pathway activity. These results demonstrated a heterogeneity in the requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing by polymorphonuclear leukocytes among various genera of gram-negative aerobic bacilli, as well as among strains of the same species. In addition, the results suggested that a mechanism of classical pathway activation dependent upon minimal immunoglobulin participates in phagocytosis and intracellular killing of certain gram-negative aerobic bacilli.

Complement Activation↗
PubMed1980

Alternative and classical complement pathway activity in sera from colostrum-fed and colostrum-deprived neonatal pigs.

Haemolytic assays were used to compare alternative and classical complement (C) pathway activities in sera obtained from neonatal pigs reared on porcine colostrum, bovine colostrum or an immunoglobulin-free synthetic diet. Dramatic increases in immunoglobulin concentrations were noted in the colostrum-fed animals during the first day of life, but there was not a concurrent, marked increase in either classical or alternative C pathway activity. Whether fed on homologous or heterologous colostrum, neonatal pigs had a similar gradual increase in alternative and classical C pathway activity in the post-natal period. If direct passive absorption of C components occurs in newborn pigs, it has only a minor influence on functional levels of alternative and classical C pathway activity in their sera. In pigs fed homologous and heterologous colostrum there was, respectively, an 83% and 80% increase in classical pathway activity, but only a 13% and 12% increase in alternative pathway activity during the first 3 days of life. Pigs fed the immunoglobulin-free synthetic diet had a 37% increase in classical C and a 24% increase in alternative C pathway activity. Part of the increase in classical C pathway activity in the post-natal period may be caused by a stimulating factor in colostrum. Most if not all of the increase in alternative C pathway activity and some of the increase in classical C pathway activity is most likely caused by normal humoral homeostatic mechanisms in the neonatal pig.

Animals↗
PubMed1978

The organization of central auditory pathways in a reptile, Iguana iguana.

The present experiments were designed to trace the central auditory pathways in an extant reptile, the New Worlkd lizard--Iguana iguana, utilizing anterograde axonal degeneration stained by the Fink-Heimer ('67) method and the retrograde axonal transport of horseradish peroxidase (LaVail and LaVail, '74). Beginning with the projections of the auditory portion of the VIIIth nerve, the ascending pathways were traced through successive relay nuclei to the telencephalon. The auditory portion of the VIIIth nerve projects to two nuclei in the dorsomedial medulla-nucleus angularis and nucleus magnocellularis medialis. These two nuclei together with a third cll group, nucleus magnocellularis lateralis (intercalated between nucleus angularis and nucleus magnocellularis medialis), have been referred to as the auditory tubercle in previous studies (cf. Miller, '75). The axonal degeneration following large lesions of the auditory tubercle and small lesions of nucleus angularis demonstrated the second order auditory pathways. Fibers leave nucleus angularis ventrally and travel to the ventral surface of the medulla where they cross the midline and ascend to the midbrain in pathways resembling the trapezoid body and the lateral lemniscus of mammals. Along these pathways, terminal arborizations of some fibers were seen in three lower brainstem nuclei while other fibers ascent to the midbrain and terminate in the central nucleus of the torus semicircularis. Experiments in which horseradish peroxidase injections were made in the torus semicircularis demonstrated that nucleus angularis is a primary source of second order auditory fibers to the midbrain and, in addition, that two of the lower brainstem targets of the auditory tubercle project to the torus semicircularis. These lower brainstem pathways were shown to be associated with the auditory system by electrophysiologically recording sound-evoked responses from clusters of cells in the torus semicircularis. Ascending fibers arising from the central nucleus of the torus semicircularis were followed rostrally where they entered the dorsal thalamus and terminated throughout nucleus medialis. Finally, a thalamotelencephalic auditory pathway was traced from nucleus medialis into the lateral forebrain bundle. Terminations of this pathway from nucleus medialis were seen in the medial dorsal ventricular ridge and in the striatum. It was concluded that the ascending auditory pathways of the iguana bear a remarkable resemblance to both the mammalian and avian auditory pathways from the level of the first order neurons in the VIIIth nerve to the level of the telencephalon. At the same time, there are important specializations of the auditory system in birds and mammals such as the development of particular lower brainstem nuclei. Nevertheless, a basic plan for the organization of the auditory system in terrestrial vertebrates can be recognized which invites comparisons with the vertebrate classes that remained in aquatic habitats...

Animals↗
PubMed1981

Substrate pathways demonstrated by transplanted Mauthner axons.

A substrate pathway is a set of aligned guidance cues. (Such cues may be either cells or molecules.) CNS substrate pathways can be demonstrated by transplanting axons to different starting locations. The stereotyped routes of transplanted axons will then demonstrate the locations of effective substrate pathways. To map CNS substrate pathways, Mauthner axons were transplanted to various unnatural locations along the CNS of Xenopus embryos. The routes of 24 experimental Mauthner axons were traced. Twenty-one of these axons grew along parts of a stereotyped route extending in the ventral marginal zone from the caudal diencephalon through the spinal cord. This ventral substrate pathway ran the length of the basal plate; thus, we call it a basal substrate pathway. One experimental Mauthner axon grew along the alar substrate pathway previously demonstrated by transplanted optic axons. The demonstrations of the alar and the basal substrate pathways suggest that during development a few long substrate pathways organize the overall layout of the long tracts of the CNS. We propose that the pattern of the earliest CNS substrate pathways is established in the neural plate and is topologically preserved as the neural plate rolls into a neural tube. This pattern may be manifest as the three-dimensional organization of the early marginal zones formed by the peripheral processes (the endfeet) of certain developing ependyma and radial glia. Subsequently, the detailed anatomy of the axon tracts and the specific terminations of individual axons are probably determined by other local chemical cues.

Brain↗
PubMed2006

[Clinical pathways. Implementation in a urological department].

BACKGROUND: Clinical pathways are directions for standardised treatment processes for different diseases or procedures in a hospital. These pathways are developed within a team of several professions and are used as order and procedure sheets. Experiences with this element of quality management are limited in Germany. METHODS: The development and the implementation process of 15 pathways in a urological department are described. A clinical pathway for female incontinence surgery (suburethral tape) is presented as an example. The effects of the pathways are evaluated on a routine basis. RESULTS: Seventy-two percent of the patients were treated according to a clinical pathway. The advantages of clinical pathways are a better structuring and transparency of medical processes, a reduction of documentation, improvements in medical education and savings in time, hospital stay of the patients and costs. Expenses for pharmaceuticals were significantly reduced in connection with development of the pathways. CONCLUSIONS: The implementation of clinical pathways is a complex but rewarding project. It can be expected that clinical pathways will be rapidly distributed in the near future and that they will contribute to improvements of health care quality.

Critical Pathways↗
PubMed1989

Concealed anterograde accessory pathway conduction during the induction of orthodromic reciprocating tachycardia.

The purpose of this study was to determine whether concealed anterograde accessory pathway conduction occurs during the induction of orthodromic tachycardia by an atrial extrastimulus (S2). Sixteen patients with an overt (n = 9) or concealed (n = 7) accessory pathway had inducible orthodromic tachycardia by S2 during an atrial drive (S1) cycle length of 500 to 650 ms. A ventricular extrastimulus (S3) was introduced coincident with the His depolarization resulting from S2 during the longest S1S2 interval that reproducibly induced orthodromic tachycardia. The S1S3 interval was decreased in 10 ms steps until S3 reached ventricular refractoriness. Retrograde accessory pathway conduction of S3 in the presence and absence of S2 was compared at the same S1S3 intervals. In the absence of S2 there was retrograde accessory pathway conduction after S3 in each patient. In the presence of S2, in patients with overt pre-excitation, retrograde accessory pathway conduction after S3 was absent in one patient, prolonged in four patients and present only after long S1S3 intervals in three patients. Only one patient had unchanged retrograde conduction regardless of the presence or absence of S2. In patients with a concealed accessory pathway, retrograde accessory pathway conduction after S3 was absent in five patients and was prolonged in two. Thus, concealed anterograde accessory pathway conduction was present in 15 of 16 patients at the time of orthodromic tachycardia induction. In conclusion, concealed anterograde accessory pathway conduction occurs in a majority of patients with an overt or a concealed accessory pathway during induction of orthodromic tachycardia by an atrial extrastimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Use of critical pathways to improve the care of patients with acute myocardial infarction.

PURPOSE: While critical pathways have become a popular strategy to improve the quality of care, their effectiveness is not well defined. The objective of this study was to investigate the effect of a critical pathway on processes of care and outcomes for Medicare patients admitted with acute myocardial infarction. SUBJECTS AND METHODS: A retrospective cross-sectional and longitudinal cohort study was made of Medicare patients aged 65 years and older hospitalized at 32 nonfederal Connecticut hospitals with a principal diagnosis of myocardial infarction during two periods: June 1, 1992, to February 28, 1993, and August 1, 1995, to November 30, 1995. The main endpoints of the cross-sectional analyses for the 1995 cohort were the proportion of patients without contraindications who received evidence-based medical therapies, length of stay, and 30-day mortality. Hospitals with specific critical pathways for patients with myocardial infarction were compared with hospitals without critical pathways. The main endpoints of the longitudinal analyses were change between 1992-93 and 1995 in the proportion of patients receiving evidence-based medical therapies, length of stay, and 30-day mortality. RESULTS: Ten hospitals developed critical pathways between 1992-93 and 1995. Eighteen of 22 nonpathway hospitals employed some combination of standard orders, multidisciplinary teams, or physician champions. Patients admitted to hospitals with critical pathways did not have greater use of aspirin within the first day, during hospitalization, or at discharge; beta-blockers within the first day or at discharge; reperfusion therapy; or use of angiotensin-converting enzyme inhibitors at discharge in 1995. The mean (+/- SD) length of stay in 1995 was not significantly different between pathway (7.8 +/- 4.6 days) versus nonpathway hospitals (8.0 +/- 4.2 days), and the change in length of stay between 1992-93 and 1995 was 2.2 days for pathway hospitals and 2.3 days for nonpathway hospitals. Patients admitted to critical pathway hospitals had lower 30-day mortality in 1995 (8.6% versus 11.6% for nonpathway hospitals, P = 0.10) and in 1992-93 (12.6% versus 13.8%, P = 0.39), but the differences were not statistically significant. CONCLUSIONS: Hospitals that instituted critical pathways did not have increased use of proven medical therapies, shorter lengths of stay, or reductions in mortality compared with other hospitals that commonly used alternative approaches to quality improvement among Medicare patients with myocardial infarction.

Aged↗
PubMed2000

Activation of renal afferent pathways following furosemide treatment. II. Effect Of angiotensin blockade.

The goal here and in the accompanying paper was to evaluate the two pathways used by the kidney to provide information to the central nervous system (CNS); e.g., the indirect, hormonal route via activation of the renin-angiotensin system and the direct pathway via activation of sympathetic afferents in the caudal thoracic spinal cord. Here, three experiments were designed to evaluate the actions of angiotensin elicited by subcutaneous injection of furosemide on neural activation of the CNS. The number of neurons immunocytochemically staining for the protein product (Fos) of the c-fos gene was used as an index of neuronal activation. In the first experiment, furosemide injection was preceded by treatment with a dose of Captopril, CAP, (an angiotensin-converting enzyme (ACE) inhibitor) that blocks the peripheral but not the central formation of angiotensin II. In the second experiment, furosemide injection was preceded by treatment with a higher dose of CAP; this dosage blocks the peripheral and central formation of angiotensin II. In the third experiment, furosemide injection was preceded by treatment with Losartan, a competitive receptor antagonist of type I angiotensin II receptors at a dose that would block central and peripheral angiotensin receptors. Control animals in each experiment received injections of vehicle (sterile isotonic saline) instead of furosemide. In each experiment, rats were sacrificed 1.75 h following furosemide or saline injection by transcardial perfusion and tissues were immunocytochemically processed for demonstration of Fos antigen. Rats receiving furosemide plus the low CAP dose showed more Fos-positive cells than control rats in the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), supraoptic nucleus (SON), magnocellular region of the paraventricular nucleus, nucleus of the solitary tract (NTS), and caudal thoracic/rostral lumbar spinal cord dorsal horn. Rats receiving furosemide plus Losartan or furosemide plus the higher CAP dose did not show increased Fos immunoreactivity in any of the abovementioned structures relative to their respective control animals. We conclude that the receptor-mediated action of angiotensin II is in some way involved in the activation of the pathway that occurs in the SFO, OVLT, SON, and magnocellular region of the paraventricular nucleus (PVN) in response to furosemide treatment. It is possible that the furosemide-induced activation in the SON and PVN is not due to direct actions of angiotensin II on angiotensin receptors in those structures, but instead occurs synaptically as a result of inputs from the SFO and OVLT, which have themselves been activated directly by angiotensin II. In the accompanying paper, furosemide-induced activation in the NTS and caudal thoracic spinal cord is abolished by prior bilateral renal denervation, meaning that these neurons are likely part of a renal afferent pathway. Here, these structures did not elaborate Fos in animals injected with furosemide plus the high CAP dose or furosemide plus Losartan. Thus, the present results also suggest that the central blockade of the formation of angiotensin II or blockade of the actions of angiotensin II prevents in some way the activation of the renal afferent pathway mediated by the renal nerves (the direct pathway) in response to the actions of furosemide. Therefore, these results suggest that central angiotensin II is somehow involved in "priming" or increasing the sensitivity of the direct renal afferent pathway. Taken together with the accompanying paper, our results indicate that interruption of the direct pathway via renal denervation did not interfere with the elaboration of Fos in the lamina terminalis; in contrast, modification of the humoral renal afferent pathway can affect the sensitivity of the direct pathway. These results may have important implications for pathophysiological changes associated with fluid balance disorders including renal hypertension.

Afferent Pathways↗
PubMed2001

The role of a nurse case manager in implementing a critical pathway for infrainguinal bypass surgery.

BACKGROUND: A previous study showed the effectiveness of a clinical pathway for infrainguinal bypass surgery in reducing postoperative length of stay (LOS) in an acute care setting. Most of the deviations from the pathway were due to patient factors (50%) and/or external disposition problems (30%), but 20% were related to physician or system problems that could potentially be modified. The current study examined those factors influencing LOS following infrainguinal bypass surgery and the impact of daily rounds by a nurse case manager--a vascular nurse specialist--on LOS and pathway deviations. METHODS: Data were collected through detailed chart review and prospective tracking of pathway deviations. LOS was compared in 58 patients on the modified pathway (with the nurse case manager) to 69 patients on the original pathway and 67 prepathway controls. Multivariate analysis was used to identify factors influencing postoperative LOS and to compare LOS among the three groups. RESULTS: Use of a nurse case manager significantly reduced physician-related deviations, from the pathway from 10% to 0% (p = .015), and reduced system-related deviations from 3% to 0%. Median postoperative LOS was 7 days before the pathway was begun, 6 days with the original pathway, and 5 days after the introduction of a vascular nurse specialist (p = .0001). There were no differences in rates of complications, rates of readmission, or mortality. CONCLUSIONS: Intervention by a nurse case manager facilitated implementation of a critical pathway for patients undergoing infrainguinal bypass surgery, especially by preventing patient deviations due to intrainstitutional factors.

Aged↗
PubMedDate not supplied

Use of a critical pathway for colon resections.

Tremendous variation in patient care exists, both among medical centers and among individual surgeons, in the field of colon and rectal surgery. Clinical or critical pathways based on "best demonstrated practices" from the medical literature have led to improved outcomes for many disease entities. The objective of this study was to develop a pathway for elective colon and rectal resections, and then determine whether this led to any improvement in measurable outcomes. A critical pathway was developed for the care of patients undergoing elective colon and rectal surgery, by reviewing best demonstrated practices in the literature and then developing standardized order sheets, nursing flow sheets, and patient educational material. A patient satisfaction survey was also included in the evaluation process. After being informed of the positive results from the pilot study, surgeons were encouraged to use the critical pathway order sheets, patient information sheets, and flow sheets for their patients undergoing elective abdominal colon or rectal surgery. Between January 1995 and October 1998, the critical pathway was used for 263 patients, whereas for 122 patients this pathway was not used. For those patients in the critical pathway group, the hospital length of stay was shorter (5.5 vs. 8.2 days, including the day of surgery, P = 0.001), the time until a regular diet was tolerated was shorter (3.5 vs. 4.4 days, P = 0.001), the percentage of patients discharged home was greater (90% vs. 82%, P = 0.038), and the average hospital charges were less (12,672 dollars vs. 16,665 dollars, P = 0.001). These advantages did seem to be correlated with efforts at postoperative ambulation, but were independent of the type of postoperative pain control (patient-controlled analgesia vs. epidural analgesia). Patient satisfaction in the subset surveyed was slightly better for those in the critical pathway group than in those for whom the critical pathway was not used. Elective colon and rectal surgery appears to lend itself to uniformity of postoperative order sheets and clinical expectations. Shortened lengths of hospital stay, earlier resumption of a regular diet, and diminished hospital charges were found with the use of this critical pathway, with no diminution of patients' perceptions of satisfaction with the hospital experience.

Adult↗
PubMed1985

Effect of plasma levels of parathyroid hormone on NADPH pathways in kidney and liver.

NADPH available for mixed function oxidations (pathway 1) or biosynthetic processes (pathway 2) has been evaluated in different cells from rat liver and kidney. In addition, changes of the proportion of NADPH utilized in each pathway were demonstrated in the same cells from rats showing different circulating levels of parathyroid hormone (PTH). Quantitative levels of NADPH directed into each of these pathways have been measured and histologically located in sections from rat liver and kidney using quantitative cytochemistry and scanning and integrating microdensitometry. Centrilobular hepatocytes utilize the major amount of NADPH, either via pathway 1 or 2. Kidney cells utilize most NADPH via pathway 2, particularly in the distal part of the nephron. The cells of the pars recta have shown the highest capacity to utilize NADPH via pathway 1, which is about half that of centrilobular hepatocytes. In centrilobular cells, the presence of high plasma levels of PTH results in a significant increment of NADPH utilization either via pathway 1 or 2. In kidneys from rats showing high plasma levels of PTH, a selective increase in NADPH utilized via pathway 2 was observed in the distal convoluted tubule whereas a selective increase in NADPH utilized via pathway 1 was demonstrated in cells of the pars recta. These observations provide further information in the understanding of the physiology of kidney and liver cells.

Animals↗
PubMed1980

The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus.

The native capsular polysaccharide antigen of type III, group B Streptococcus contains a terminal sialic acid residue on each repeating unit that masks all end-group galactopyranose residues and prevents alternative pathway complement activation by adult human sera in the absence of type-specific antibody. The critical role of the sialic acid residues in allowing the organism to evade activating the alternative complement pathway was shown when neuraminidase treatment of the organism converted the bacteria to activators of the alternative pathway as assessed in agammaglobulinemic serum. The requirement for specific antibody in permitting alternative pathway activation by the fully sialated bacteria was shown when sera that contained low levels of specific antibody failed to activate this pathway, and when prior absorption of serum that contained higher type-specific antibody levels with the capsular antigen failed to activate this pathway. The use of C2-deficient sera showed that the calssical pathway was not required for antibody-dependent alternative pathway activation. The use of isotonic, pH 7.5, veronal-NaCl buffer that contained 1% gelatin and that was supplemented to 4 mM Mg++ and 16 mM EGTA and adjusted to pH 7.5 (MgEGTA) ruled out the participation of the C1-bypass pathway. The presence of sialic acid on the bacterial surface is one means of evading an important mechanism of natural immunity, namely activation of complement by the alternative pathway. Only specific antibody, i.e., acquired immunity, can overcome this virulence factor.

Antibodies, Bacterial↗
PubMed2001

Managing patients with acute, nonvariceal gastrointestinal hemorrhage: development and effectiveness of a clinical care pathway.

OBJECTIVES: To develop a clinical care pathway for the management of patients with acute upper or lower nonvariceal GI hemorrhage (GIH) who do not require immediate surgical intervention. To test the effectiveness and safety of the pathway in improving the efficiency of care for patients with acute GIH. METHODS: A multidisciplinary team developed the evidence-based GIH clinical care pathway by consensus techniques. In a quasiexperimental design, pathway outcomes were measured prospectively during the first 8 months of pathway implementation, and compared to similar time periods in the 2 prior yr. Effectiveness measures were the number of patients <65 yr of age admitted for GIH and the hospital length of stay for all patients. Thirty-day safety outcomes were the rates of recurrent GIH, mortality, and readmission to hospital for any reason. RESULTS: Of 368 patients studied after pathway implementation, 81 (22%) were managed as outpatients. The number of admissions for pathway patients <65 yr of age was significantly lower compared to 691 prepathway patients (p < 0.002). Mean length of stay (+/- 95% CI) for pathway inpatients was 3.5 (3.1, 3.9) days, compared to 5.3 (4.9, 5.7) and 4.6 (4.2, 5) days in the 2 prepathway yr, respectively (p < 0.001). Multivariable regression controlling for admission vital signs, comorbid conditions, age, and the etiology of GIH confirmed that admission after pathway implementation was an independent predictor of a reduced length of hospital stay. There were no significant between-year differences in the 30-day rates of recurrent GIH, mortality, or hospital readmission. CONCLUSION: A multidisciplinary clinical care pathway may improve the efficiency of caring for patients with acute upper or lower nonvariceal GIH. Decreasing the number of admissions for GIH and reducing the hospital length of stay can be achieved without increasing the number of adverse outcomes.

Acute Disease↗
PubMed1998

Impact of clinical pathways and practice guidelines on the management of acute exacerbations of bronchial asthma.

OBJECTIVES: In 1990, it was estimated that approximately 1% of all US health-care costs (approximately $6.2 billion) were spent on asthma-related health expenses. Of this, hospitalization charges alone exceeded $2.6 billion. Practice guidelines and clinical pathways are being developed to standardize the management of acute asthma with the aim of improving care and safely reducing health-care costs. In this report, we evaluate the impact of an asthma pathway developed and instituted at a large community-based teaching hospital. This pathway was evidence based and was developed by a multidisciplinary group. METHODS: The study was conducted during a 6-month period in 1995, while a similar period in 1994 was used as a historical control period. Data collected included patient demographics, hospital admission and discharge peak expiratory flow rates, pulse oximetry measurements, length of stay, conversion from hand-held nebulizer to metered-dose inhaler, use of corticosteroids within 24 h of hospitalization, and conversion of i.v. steroids to oral steroids. RESULTS: A total of 42 patients were enrolled during the study period. Of these, 19 were placed on the pathway, while 23 were not treated according to the pathway. There were 38 patients in the 1994 historical control period. For 1995, there was no significant difference between the pathway and nonpathway groups with regard to the length of stay (4.4+/-3.3 vs 3.2+/-2.3 days; p > 0.05), hospital discharge peak expiratory flow rates (324 vs 286 L/min; p > 0.05), or use of steroids (100% vs 91%; p > 0.05). However, a significant increase in conversion from hand-held nebulizer to metered-dose inhaler was noted in the pathway group (68% vs 34%; p < 0.05). The data from 1994 compared to 1995 pathway were similar in that there was no difference in the length of stay (3.4+/-2.1 vs 4.4+/-3.3 days; p > 0.05) and/or use of steroids (92% vs 100%; p > 0.05), while a significant increase in hand-held nebulizer to metered-dose inhaler conversion was observed for the 1995 pathway group (68% vs 26%; p=0.002). CONCLUSIONS: We conclude that although the asthma pathway did not significantly reduce length of stay, it was associated with a significant increase in hand-held nebulizer to metered-dose inhaler conversion, resulting in a substantial cost savings of $288,000/year.

Acute Disease↗