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Knowledge, expectations, and inductive reasoning within conceptual hierarchies.

Previous research (e.g. Cognition 64 (1997) 73) suggests that the privileged level for inductive inference in a folk biological conceptual hierarchy does not correspond to the "basic" level (i.e. the level at which concepts are both informative and distinct). To further explore inductive inference within conceptual hierarchies, we examine relations between knowledge of concepts at different hierarchical levels, expectations about conceptual coherence, and inductive inference. In Experiments 1 and 2, 5- and 8-year-olds and adults listed features of living kind (Experiments 1 and 2) and artifact (Experiment 2) concepts at different hierarchical levels (e.g. plant, tree, oak, desert oak), and also rated the strength of generalizations to the same concepts. For living kinds, the level that showed a relative advantage on these two tasks differed; the greatest increase in features listed tended to occur at the life-form level (e.g. tree), whereas the greatest increase in inductive strength tended to occur at the folk-generic level (e.g. oak). Knowledge and induction also showed different developmental trajectories. For artifact concepts, the levels at which the greatest gains in knowledge and induction occurred were more varied, and corresponded more closely across tasks. In Experiment 3, adults reported beliefs about within-category similarity for concepts at different levels of animal, plant and artifact hierarchies, and rated inductive strength as before. For living kind concepts, expectations about category coherence predicted patterns of inductions; knowledge did not. For artifact concepts, both knowledge and expectations predicted patterns of induction. Results suggest that beliefs about conceptual coherence play an important role in guiding inductive inference, that this role may be largely independent of specific knowledge of concepts, and that such beliefs are especially important in reasoning about living kinds.

Adolescent↗

Fractional analysis of sequential induced sputum samples during sputum induction: evidence that different lung compartments are sampled at different time points.

BACKGROUND: The effect of the duration of sputum induction on markers of inflammation in induced sputum is unknown, and the optimal duration of sputum induction for research purposes in airway disease is uncertain. OBJECTIVE: We sought to determine whether the duration of sputum induction influences the cellular or biochemical characteristics of induced sputum. METHODS: Induced sputum was collected sequentially at 4-minute intervals during a 20-minute sputum induction in 12 subjects with mild and moderate asthma. Each 4-minute sample was collected and analyzed separately for total and differential cell counts and for levels of eosinophil cationic protein, fibrinogen, mucin-like glycoprotein, and surfactant protein SP-A. RESULTS: The percentages of eosinophils and neutrophils were significantly higher at the beginning of the 20-minute sputum induction than at the end, whereas the percentage of macrophages was significantly lower at the beginning than at the end. In addition, the levels of eosinophil cationic protein and mucin-like glycoprotein were significantly higher at the beginning of the 20-minute induction than at the end, whereas the level of surfactant protein SP-A was significantly lower. CONCLUSIONS: The duration of sputum induction significantly affects the cellular and biochemical composition of induced sputum in a manner suggesting that large airways are sampled at the beginning of sputum induction, whereas peripheral airways and alveoli are sampled at later time periods. Our data demonstrate the importance of standardizing the duration of sputum induction in clinical research studies, and on the basis of these data, we have chosen 12 minutes as the optimal duration for sputum induction in asthmatic subjects.

Adult↗

Characterization of the promoter regions involved in galactose- and nisin-mediated induction of the nisA gene in Lactococcus lactis ATCC 11454.

The nisA promoter is positively regulated in Lactococcus lactis ATCC 11454 by autoinduction via a two-component NisRK-mediated system. However, induction of this promoter can also occur when introduced into the plasmid-free L. lactis LM0230 during growth in galactose or lactose, independent of the NisRK system. In this study, we also characterized this galactose-mediated induction by determining the nisA start site during growth in galactose, which was identical to the nisA start site upon nisin induction. The region involved in the galactose-mediated induction of the nisA promoter was investigated by directed deletion analysis of a 200 bp region upstream of the nisA promoter in the transcription fusion pDOC99. The induction of the deletion derivatives by galactose and nisin was compared phenotypically using beta-galactosidase measurements, and the regions necessary for the induction were determined by sequence analysis. Analysis of these regions revealed two sets of a TCT direct repeat [TCT-N8-TCT] present at positions (-107 to -94) and (-39 to -26) relative to the transcription initiation site. Disruption of the upstream repeat abolished galactose induction and significantly reduced the nisin induction capacity, suggesting a potential pivotal role for these repeats in transcription induction of the nisA promoter. It was also observed that the galactose-mediated induction was abolished when a plasmid containing the phosphotransferase system (PTS), phospho-beta-galactosidase and tagatose pathway genes was introduced into this strain. As this effectively made the Leloir pathway redundant, it points to some component of this pathway as the specific inducer of the nisA promoter.

Bacterial Proteins↗

Perioperative anxiety and postoperative behavioural disturbances in children undergoing intravenous or inhalation induction of anaesthesia.

BACKGROUND: There are few published data comparing the psychological effects of intravenous (i.v.) and inhalation methods of anaesthesia induction in children. In the present study, we compared perioperative anxiety and postoperative behavioural changes in children undergoing standardized i.v. induction with thiopental and inhalation induction with sevoflurane for routine ear, nose and throat surgery. METHODS: Children were randomly assigned to receive inhalation induction with sevoflurane or i.v. induction with thiopental. Anxiety was assessed on arrival, at induction and 30 min after transfer to the recovery room using a four-point scale. The incidence of postoperative behavioural disturbances was determined using a postoperative questionnaire. RESULTS: Significantly more children were anxious during induction in the i.v. group than in the inhalation group [23 of 50 (46%) versus 5 of 50 (10%); P = 0.0001]. Mean induction time was shorter (5.6 versus 7.0 min; P = 0.0001) and recovery time longer (30.5 versus 10.4 min; P = 0.0001) in the i.v. group compared with the inhalation group. Problematic behavioural changes were reported in the first 2 weeks after surgery in nine of 32 children (28%) in the i.v. group and 16 of 34 (48%) children in the inhalation group (P = 0.13). CONCLUSIONS: Although children were more anxious during i.v. induction than inhalation induction, there was no difference in the incidence of behavioural disturbances in the first 2 weeks postoperatively.

Adolescent↗

Sevoflurane-fentanyl versus etomidate-fentanyl for anesthetic induction in coronary artery bypass graft surgery patients.

OBJECTIVE: To compare the hemodynamic effects of sevoflurane-fentanyl with etomidate-fentanyl during anesthetic induction in patients with coronary artery disease with good left ventricular function. DESIGN: A prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were allocated randomly to receive either 4% sevoflurane/nitrous oxide 67%/oxygen 33% (sevoflurane group) or etomidate, 0.2 mg/kg, for induction (intravenous group). Both techniques were supplemented by 10 microg/kg of fentanyl and muscle relaxation with pancuronium. Anesthesia was maintained in both groups with 2% sevoflurane/nitrous oxide 67%/oxygen 33%. MEASUREMENTS AND MAIN RESULTS: Time to loss of consciousness and airway complications during induction were assessed. Hemodynamics were recorded at 1-minute intervals during the induction period up to 5 minutes postintubation. Induction of anesthesia was significantly faster in patients given etomidate compared with patients who received sevoflurane; loss of eyelid reflex was 45 seconds (standard deviation 17 seconds) versus 97 seconds (standard deviation 20 seconds). None of the patients who received sevoflurane had airway complications during the induction period. Both anesthetic induction techniques provided cardiostability with little change in cardiac index (2%). The decrease in mean arterial blood pressure was greater in the patients who received sevoflurane induction (maximal decrease 28% v 14%). The heart rate and filling pressure changes were insignificant. CONCLUSION: Sevoflurane inhalation induction produced minimal changes in cardiac index and no airway complications in patients with coronary artery disease with good left ventricular function. Induction was faster with etomidate, however, and blood pressure remained higher.

Anesthesia, General↗

[Minimal residual disease analysis in acute lymphoblastic leukemia of childhood within the framework of COALL Study: results of an induction therapy without asparaginase].

UNLABELLED: The detection of minimal residual disease (MRD) is a major prognostic factor for treatment in acute lymphoblastic leukemia (ALL) of childhood. Several groups showed the predictive value of MRD after 5 weeks of chemotherapy (at the end of induction therapy). Patients with more than 1 leukemic cells in 100 cells (> or = 10(-2)) at this time-point have a significantly higher relapse rate. The MRD measurement has been shown to be an independent prognostic factor at several time points in the BFM study (ALL-BFM 90) as well as in the EORTC study. The aim of our investigations was the detection of MRD at the end of induction therapy within the COALL studies which is different from the above studies. In the COALL studies, therapy starts with a 1 week DNR prephase (24 h infusion on day one) and i.th. MTX. Induction therapy consisted of 3 drugs over a period of 4 weeks (Prednisolone, Vincristine and Daunorubicin), asparaginase is given later in consolidation. At the end of induction therapy, bone marrow was obtained for cytomorphologic and molecular analysis. PATIENTS AND METHODS: We investigated bone marrow samples from 76 patients. All patients were in morphologic remission at the end. of induction therapy. For MRD analysis, DNA was isolated from bone marrow mononuclear cells. Clonal T-cell-receptor (TCR) or immunoglobulin gene (IgH) rearrangements were identified by PCR. Monoclonal products were either sequenced directly (TCR) or after excision from high resolution agarose gels. Subsequently patient-specific oligonucleotides for allele-specific PCR were generated. PCR analysis was performed with 1 microgram DNA for each reaction within a semiquantitative matter. This method reached sensitivities down to 10(-5). RESULTS: Eighty-four percent of the analysed samples were MRD positive at the end of induction therapy. 20 out of 76 patient samples (26%) were highly positive (> or = 10(-2)), 28 patients had levels of about 10(-3) (37%), 16 had levels around 10(-4) (21%) and 12 patients had no detectable residual cells (16%). All analysed 15 T-ALL patients had detectable residual disease at this timepoint. Until now, 5/20 patients with very high MRD level at the end of induction therapy suffered a relapse. DISCUSSION: Patients with very high MRD level at the end of induction therapy showed an elevated risk of relapse, but the predictive value is much poorer than for example in the BFM 90 MRD-study. We suggest, that a high MRD level at this timepoint results from a different induction therapy compared to the BFM 90 study. In the COALL studies asparaginase is given only after induction therapy to decrease the risk of thrombosis. We would like to conclude that this differences were compensated later during therapy as the event free survival of both studies is similar. In conclusion, an optimal information from MRD studies is strongly associated with the given therapy. Therefore we initiated an additional MRD time-point after the first chemotherapy block in consolidation.

Antineoplastic Combined Chemotherapy Protocols↗

[Shorter delivery time after induction with misoprostol].

INTRODUCTION: Increasing evidence has demonstrated that intravaginal misoprostol (PGE1) is more effective in labor induction than dinoprostone (PGE2). Several studies have demonstrated that the administration of PGE1 instead of PGE2 reduces the induction-to-delivery interval. However, it has not been fully investigated on which phase of birth the activity of PGE1 is stronger than that of PGE2. We undertook this study to investigate whether the activity of the two prostaglandins are different over time during the induction-to-delivery interval. MATERIAL AND METHODS: 155 patients undergoing induction of labor with 50 micrograms intravaginal PGE1 were compared with 174 patients treated with 3 mg PGE2. In both groups the procedure was repeated 6, and 24 hours after the first dose until labor was achieved. Induction-to-initiation of labor time, duration of labor stages, induction-to-delivery time, mode of delivery, maternal and neonatal morbidity and changes in Bishop score were compared. RESULTS: Demographic characteristics, indications for induction, mode of delivery, fetal weight, maternal and neonatal morbidity and duration of the labor stages were similar between the groups. A significant difference was found in terms of: induction-to-initiation of labor interval (7.37 h [1-68] vs. 11.25 h [1-74], p < 0.01) and induction-to-delivery interval (11.5 h [2.5-89] vs. 14.4 h [2.7-94], p < 0.05). The Bishop score at the time of the second administration was significantly different from that at admission in the PGE1 group compared to the PGE2 group [PGE1: 4.8 +/- 2/5.6 +/- 1.9, p < 0.0005; PGE2: 3.9 +/- 2/4.2 +/- 1.4, p = 0.09]. This effect of PGE1 remained significant after correction for various explanatory variables. CONCLUSIONS: The stronger effect of PGE1 is the consequence of a faster cervical ripening, which in turn leads to a quicker achievement of active labor. DISCUSSION: Intravaginal PGE1 compared to PGE2 reduces significantly the induction-to-delivery time.

Administration, Intravaginal↗

Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group.

BACKGROUND: As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another. METHODS: We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment. RESULTS: The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked "nothing" about their treatment than those in the expectant-management groups. CONCLUSIONS: In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.

Adult↗

Sputum induction problems identified through genetic fingerprinting.

OBJECTIVE: To identify the contamination source of a cluster of eight positive Mycobacterium tuberculosis isolates from one laboratory session. METHODS: Spoligotyping was performed on M. tuberculosis isolates processed during one laboratory session. Laboratory and sputum induction protocols and records were reviewed. Sputum induction staff were interviewed. An environmental assessment of the sputum induction booth was performed. RESULTS: Spoligotyping identified a unique strain of susceptible M. tuberculosis from five induced sputa collected at Clinic A on the same day. Three specimens processed concurrently from other clinics had spoligotypes different from each other and from the cluster strain. A laboratory investigation revealed no procedural lapses. Sputum induction records from Clinic A indicated that patient 1 in the sputum induction booth had prior culture-confirmed tuberculosis. Patient 2 had a history of a drug-resistant strain. Patient 3 had completed tuberculosis treatment, with positive cultures 7 months earlier. Patients 4 and 5 were new to the clinic and had no subsequent positive M. tuberculosis specimens. The sputum induction booth was working within normal parameters. Sputum induction that day was overseen by a new employee with limited training and no supervision. A review of the sputum induction protocol identified ambiguity regarding care of the ultrasonic nebulizer between patients, which may have led to reuse of the discarded nebulizer solution from patient 1. CONCLUSIONS: A break in the sputum induction protocol may have contributed to contamination of patient specimens. Sputum induction is complicated, mandating adequate staff training and supervision and patient preparation. Spoligotyping identified a potential source of M. tuberculosis contamination.

Clinical Laboratory Techniques↗

Nitric oxide mediates apoptosis induction selectively in transformed fibroblasts compared to nontransformed fibroblasts.

Nitric oxide (NO) mediates apoptosis induction in fibroblasts with constitutive src or induced ras oncogene expression, whereas nontransformed parental cells and revertants are not affected. This direct link between the transformed phenotype and sensitivity to NO-mediated apoptosis induction seems to be based on the recently described extracellular superoxide anion generation by transformed cells, as NO-mediated apoptosis induction in transformed cells is inhibited by extracellular superoxide dismutase (SOD), by SOD mimetics and by apocynin, an inhibitor of NADPH oxidase. Furthermore, nonresponsive nontransformed cells can be rendered sensitive for NO-mediated apoptosis induction when they are supplemented with xanthine oxidase/xanthine as an extracellular source for superoxide anions. As superoxide anions and NO readily interact in a diffusion-controlled reaction to generate peroxynitrite, peroxynitrite seems to be the responsible apoptosis inducer in NO-mediated apoptosis induction. In line with this conclusion, NO-mediated apoptosis induction in superoxide anion-generating transformed cells is inhibited by the peroxynitrite scavengers ebselen and FeTPPS. Moreover, direct application of peroxynitrite induces apoptosis both in transformed and nontransformed cells, indicating that peroxynitrite is no selective apoptosis inducer per se, but that selective apoptosis induction in transformed cells by NO is achieved through selective peroxynitrite generation. The interaction of NO with target cell derived superoxide anions represents a novel concept for selective apoptosis induction in transformed cells. This mechanism may be the basis for selective apoptosis induction by natural antitumor systems (like macrophages, natural killer cells, granulocytes) that utilize NO for antitumor action. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression.

Animals↗

Characterization of the photosynthetic induction response in a Populus species with stomata barely responding to light changes.

The photosynthetic induction response is constrained by stomatal and biochemical limitations. However, leaves in some plants like Populus koreana x trichocarpa cv. Peace (a hybrid clone) may have little stomatal limitation because their stomata barely respond to changes in photon flux density (PFD). We examined the induction responses of leaves of well-watered and dehydrated P. koreana x trichocarpa plants grown in a high-light or a low-light regime. With an increase in PFD from 50 to 500 micromol m(-2) s(-1), steady-state stomatal conductance (g(s)) increased by only 0.25-8.2%, regardless of the initial g(s), but steady-state assimilation rate (A) increased by 550-1810%. Photosynthetic induction times required to reach 50% (IT50) and 90% (IT90) of A at high PFD were 60-90 s and 210-360 s, respectively. Examination of the dynamic relationships between A and g(s), and between A and intercellular CO2 concentration, indicated that the induction limitation was imposed completely by the biochemical components within 30-40 s after the PFD increase. Values of IT50 and IT90 were significantly higher in low-light leaves than in high-light leaves, whereas the induction state at 60 s and the induction efficiency at 60 and 120 s after the increase in PFD were lower in low-light leaves than in high-light leaves. Dehydration reduced leaf water potential (psi) significantly, resulting in a significantly decreased initial g(s). Leaf water potential had no significant effects on induction time in high-light leaves, but a low psi significantly reduced the induction time in low-light leaves. We conclude that the photosynthetic induction response was limited almost completely by biochemical components because the stomata barely responded to light changes. The biochemical limitation appeared to be higher in low-light leaves than in high-light leaves. Mild water stress may have reduced steady-state A and g(s), but it had little effect on the photosynthetic induction response in high-light leaves.

Carbon Dioxide↗

Pulmonary artery catheter placement for elective coronary artery bypass grafting: before or after anesthetic induction?

UNLABELLED: Pulmonary arterial catheters (PACs) are often used during and after coronary artery bypass grafting. We hypothesized that placement of a PAC would be faster in anesthetized patients. We further hypothesized that the presence or absence of a PAC during the induction of anesthesia would make no difference in hemodynamics, vasoactive drug use, or IV fluid administration during the induction. Patients (n = 200) undergoing elective coronary artery bypass grafting were assigned to PAC insertion either before or after the induction of anesthesia. Total time for PAC insertion, number of finder needle and venous catheter insertion attempts, incidence of carotid artery puncture, arrhythmias or ST segment changes, arterial blood gas analysis, hemodynamic variables, IV fluids, and vasoactive drugs required during and after the anesthetic induction were recorded. Thirty-two different physicians placed the PACs. PAC placement was faster (10 versus 12 min, P = 0.0003) and required fewer punctures with a finder needle (P = 0.0107) in anesthetized patients. There were no significant differences between groups in hemodynamic values or use of vasoactive or anesthetic drugs or IV fluids during the induction. There were also no significant differences between groups in the incidence of myocardial ischemia, arterial hypoxemia, or hypercarbia. Placement of a PAC before the induction of anesthesia consumes more time and fails to improve hemodynamic stability or lessen vasoactive drug use during the induction of anesthesia. IMPLICATIONS: Insertion of pulmonary artery catheters (PACs) before the induction of anesthesia requires more needle sticks and takes longer than insertion after the induction of anesthesia; moreover, previous PAC insertion has no significant effect on hemodynamics or use of vasoactive drugs or IV fluid associated with the induction of anesthesia.

Aged↗

Investigation of effective anesthesia induction doses using a wide range of infusion rates with undiluted and diluted propofol.

BACKGROUND: The influence of infusion rate on the induction dose-response relation has not been investigated over a wide range of infusion rates. In this study, the authors defined the effect of different propofol infusion rates on the times and doses necessary to reach clinical induction of anesthesia. METHODS: The subjects of the study were 250 patients classified as American Society of Anesthesiologists physical status I or II aged 25-55 yr. For induction with undiluted propofol, 180 patients were allocated randomly to one of two groups of 90 patients each (A and B). Each group was further divided into nine subgroups (10 patients each) that were administered propofol infusion at rates of 10, 15, 20, 30, 40, 60, 100, 200, and 300 mg/kg-1/h-1. The remaining 70 patients (group C) were allocated randomly into seven subgroups (10 patients each), and these groups were induced with diluted propofol (0.5 mg/ ml) at the rates of 10, 15, 30, 60, 100, 200, and 300 mg/kg-1/ h-1. Group B was given crystalloid at the same infusion rates as group C via a catheter in the opposite arm. Induction time, induction dose, plasma arterial propofol concentration at loss of consciousness, and percentage decrease of systolic blood pressure were measured. A previously reported three-compartment model with an effect-site rate constant for propofol of 0.456/min was used to predict the induction time and dose at each infusion rate. RESULTS: The differences between predicted induction time and dose and the observed time and dose could be explained by factoring in the lag time from infusion site to central compartment (lag time circulation) and the amount of propofol in transit during this time (residual dose circulation). Residual dose circulation and lag time circulation correlated with infusion time from 20 to 60 s for undiluted and from 0 to 40 s for diluted propofol. At the infusion rates greater than 80 mg/kg-1/h-1, rapid circulation because of incomplete mixing in the central compartment decreased the excess induction time and dose. The use of diluted propofol significantly attenuated the decrease in systolic blood pressure provoked by the residual dose circulation. CONCLUSIONS: Induction dose and time are dependent on infusion rate in a complex manner, and residual dose circulation was a factor in overdose and hemodynamic depression. Hypotension during induction was attenuated by diluted propofol.

Adult↗

Comparison of predicted induction dose with predetermined physiologic characteristics of patients and with pharmacokinetic models incorporating those characteristics as covariates.

BACKGROUND: The relationship between patient characteristics and anesthesia induction dose at a high administration rate is unclear. This study was designed to investigate the relation between induction dose and patient characteristics and to compare it to the predicted induction dose using the previously reported pharmacokinetic model. METHODS: Diluted propofol (0.5 mg/ml) dose required to reach loss of consciousness, when infused at an infusion rate per lean body mass (LBM) of 150 mg x kg(-1) x h(-1) (high rate), was determined in 82 patients, ages 10-85 yr. Cardiac output, blood volume, central blood volume (CBV), and hepatic blood flow were measured with indocyanine green pulse spectrophotometry. Stepwise multiple linear regression models were used to investigate the relations between the patient characteristics and induction dose. These were compared with our previously reported parameters at the rate of 40 mg x kg(-1) x h(-1) (low rate) and with predicted induction doses with two previously reported pharmacokinetic models. RESULTS: Significant factors for predicting the induction dose at a high rate were age, LBM, and CBV. Induction dose with one pharmacokinetic model was 1.5 times that of the measured one and the other was half that of the measured one at a high rate. At a low rate, one pharmacokinetic model provided an accurate induction dose. CONCLUSIONS: The prediction of induction dose from physiologic characteristics of patients provides reasonable accuracy at both high and low administration rates of propofol. A previously reported pharmacokinetic model that incorporated patient characteristics provides the same accurate induction dose at a low rate.

Adolescent↗

Factors predicting labor induction success: a critical analysis.

Because of the risk of failed induction of labor, a variety of maternal and fetal factors as well as screening tests have been suggested to predict labor induction success. Certain characteristics of the woman (including parity, age, weight, height and body mass index), and of the fetus (including birth weight and gestational age) are associated with the success of labor induction; with parous, young women who are taller and lower weight having a higher rate of induction success. Fetuses with a lower birth weight or increased gestational age are also associated with increased induction success. The condition of the cervix at the start of induction is an important predictor, with the modified Bishop score being a widely used scoring system. The most important element of the Bishop score is dilatation. Other predictors, including transvaginal ultrasound (TVUS) and biochemical markers [including fetal fibronectin (fFN)] have been suggested. Meta-analyses of studies identified from MEDLINE, PubMed, and EMBASE and published from 1990 to October 2005 were performed evaluating the use of TVUS and fFN in predicting labor induction success in women at term with singleton gestations. Both TVUS and Bishop score predicted successful induction [likelihood ratio (LR)=1.82, 95% confidence interval (CI)=1.51-2.20 and LR=2.10, 95%CI=1.67-2.64, respectively]. As well, fFN and Bishop score predicted successful induction (LR=1.49, 95%CI=1.20-1.85, and LR=2.62, 95%CI=1.88-3.64, respectively). Although TVUS and fFN predicted successful labor induction, neither has been shown to be superior to Bishop score. Further research is needed to evaluate these potential predictors and insulin-like growth factor binding protein-1 (IGFBP-1), another potential biochemical marker.

Body Weights and Measures↗

The induction of class I and II major histocompatibility complex by allogeneic stimulation is dependent on the transcription factor interferon regulatory factor 1 (IRF-1): observations in IRF-1 knockout mice.

Hosts undergoing allograft rejection show increased MHC expression locally in the graft and systemically in the normal host organs, mediated principally by IFN-gamma. The transcription factor IRF-1 has been implicated in the regulation of MHC expression by IFNs in vitro as well as in the regulation of production of some cytokines. We investigated the role of IRF-1 in vivo in the systemic regulation of MHC expression in hosts undergoing rejection of allogeneic tumors by comparing MHC induction in mice with normal IRF-1 genes (wild type or WT mice) with mice with disrupted IRF-1 genes (IRF-1 knockout or IRF-1 KO mice). We assessed MHC product expression by immunohistology and by radiolabeled antibody binding to tissue homogenates, and MHC mRNA levels by Northern blotting. By immunohistology in mice undergoing allogeneic stimulation by the ascites tumor cells, kidneys of WT mice showed massive class I and II induction, but kidneys from IRF-1 KO mice showed almost no class I and II induction. Allograft rejection also increased class I and II product levels by radiolabeled antibody binding and steady state mRNA levels, but again IRF-1 KO mice showed severe impairment of MHC induction. Similar impaired MHC class I and II induction was seen in heart and spleen, but in liver the IRF-1 mice showed impaired class I induction but unimpaired class II induction. The results indicate that IRF-1 has an essential role in both class I and class II MHC induction in allogeneic responses, but that a component of IRF-1 independent MHC induction is also demonstrable in some tissues. The reduction in MHC induction by allogeneic stimulation probably reflects decreased response to IFN-gamma and other cytokines as well as some reduction in the amount of cytokines produced.

Animals↗

The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients.

BACKGROUND: Induction therapy with daclizumab has been shown to be efficacious in the prevention of acute rejection in kidney transplant patients. The routine use of antibody induction therapy in liver transplantation has not gained widespread acceptance, except in the cases of renal insufficiency. The recent approval of daclizumab prompted us to initiate this pilot study using induction therapy in those patients at risk for developing posttransplant renal insufficiency. METHODS: This nonrandomized study examined the use of daclizumab in 39 of the last 97 liver transplants performed at the University of Alabama in Birmingham. The daclizumab group received 2 mg/kg intravenously before organ engraftment, and 38 of the 39 received 1 mg/kg intravenously on postoperative day 5. The control group consisted of the remaining 58 contemporary patients. Additional immunosuppression consisted of steroids, tacrolimus, or microemulsion cyclosporine in all patients and mycophenolate mofetil in selected patients. RESULTS: Pretransplant demographics were not significantly different between the groups. In the induction group there were significantly fewer males, 14 (36%) vs. 34 (59%) (P=0.03). They had greater renal insufficiency at the time of transplant, serum creatine 1.9+/-0.37 mg/dl vs. 0.8+/-0.5; P=0.0009, and more patients were at higher acuity (status 1 and 2A): 12 (31%) vs. 3 (5%) P=0.0006 than in the noninduction group. By postoperative day 7, renal function improved in the induction group such that it was not significantly different from the noninduction group and remained similar throughout the rest of the follow-up. The induction group also experienced significantly less acute rejection, 7 (18%) vs. 23 (40%) (P=0.02) than in the noninduction group in the first 6 months. The 1-, 3-, and 6-month patient survival rates were similar in the induction group, 97.4%, 97.4%, and 97.4%, vs. non-induction 94.8%, 93.0%, and 93% (P=NS). The incidence of cytomegalovirus, in the first 6 months, in the induction group was four (10%) vs. five (9%) (P=NS) in the noninduction group. CONCLUSION: In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.

Adult↗

Effect of alterations in early signal transduction events on the induction of procoagulant activity by murine hepatitis virus strain 3 in vitro.

The induction of macrophage procoagulant activity (PCA) has been shown to correlate with the development of fulminant hepatic necrosis after infection with murine hepatitis virus strain 3 (MHV-3). However, comparatively little is known about the early events in cells after viral infection leading to PCA expression. Accordingly, we investigated the early cellular events in the induction of macrophage PCA by MHV-3. MHV-3 stimulation of macrophages did not result in a detectable increase in intracellular calcium levels nor did stimulation of macrophages by calcium ionophores result in induction of PCA, suggesting that calcium transients were neither necessary nor sufficient for induction of PCA by MHV-3. Treatment of cells with phorbol myristate acetate had no effect on PCA induction; however, inhibition of protein kinase C (PKC) by staurosporine or H7 resulted in attenuation of macrophage PCA following MHV-3 stimulation (P < 0.05 compared with untreated macrophages), suggesting that although activation of PKC alone is insufficient for PCA induction, PKC may be an integral component of PCA induction by MHV-3. We have previously demonstrated that dimethyl prostaglandin E2 inhibited induction of PCA by MHV-3. In this study, treatment of cells by agents that increase intracellular cAMP (forskolin, isobutylmethyl xanthine) significantly inhibited PCA induction (P < 0.02). These results demonstrate that induction of macrophage PCA by MHV-3 involves PKC, but proceeds independently of changes in intracellular calcium, and that PCA expression is down-regulated by increases in intracellular cAMP.

16,16-Dimethylprostaglandin E2↗