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PubMed2007

Induction of matrix metalloproteinase gene expression in an endothelial cell line by direct interaction with malignant cells.

Mouse endothelial TKD2 cells in monolayers were cocultured with various human cell lines for 24 h, and the expression of several secreted matrix metalloproteinases (MMP) and cell adhesion molecules was examined by real-time reverse transcription-polymerase chain reaction using mouse-specific primers. Coculture with normal fibroblasts did not elicit the expression of these molecules, but coculture with cancer cells induced the expression of MMP-3, MMP-9 and MMP-10 mRNA in endothelial cells, and in normal mouse embryonic fibroblasts. The induction of MMP mRNA was dependent on direct cell adhesion, as separate culture of A549 cells in Boyden chambers did not induce MMP mRNA, and neutralizing antibody against VLA-4 abolished the induction. An inhibitor of phosphatidylinositol-3-phosphate kinase strongly suppressed the induction of MMP-3, MMP-9 and MMP-10 mRNA, and expression of the dominant-negative mutant of phosphatidylinositol-3-phosphate kinase also decreased the induction. It was suggested that intracellular reactive oxygen species (ROS) levels were increased in TKD2 cells following adhesion to cancer cells. ROS scavengers decreased the levels of MMP induction, and roterone, an inhibitor of mitochondrial complex I, strongly suppressed the induction of MMP-3, MMP-9 and MMP-10. The depletion of mitochondria in TKD2 cells decreased the induction of MMP-9, but the induction of MMP-3 and MMP-10 was not affected. These results indicate that the adhesion of cancer cells to endothelial cells activates several distinct signaling pathways to induce MMP gene expression, and the pathways for MMP-3, MMP-9 and MMP-10 are partly different. For the induction of MMP-9, mitochondria participate in induction, possibly through the production of ROS.

Animals↗
PubMed2005

Comparison of two thiopental infusion rates for the induction of anaesthesia in dogs.

OBJECTIVE: To compare the induction dose requirements of thiopental using two different infusion rates for induction of anaesthesia in dogs. STUDY DESIGN: Prospective, randomized study. ANIMALS: Fifty, healthy (ASA I or II) client-owned dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective surgery. MATERIALS AND METHODS: Animals were randomly assigned to receive an infusion of 2.5% thiopental at a rate of either 0.1 ml kg(-1) minute(-1) or 0.4 ml kg(-1)minute(-1), 30-40 minutes after pre-anaesthetic medication with intramuscular acepromazine (0.025 mg kg(-1)) and pethidine (3.5 mg kg(-1)). Thiopental administration was controlled by a precision syringe driver. Statistical analyses of the results, using the outcome 'mg kg(-1) required for induction' (log-transformed) included unpaired t-tests for all categorical data (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable linear regression for continuous variables (mass, age). All variables were then considered in a multivariable linear regression model. The quality of induction with the two different infusion rates was also assessed. RESULTS: After controlling for quality of sedation, the thiopental induction dose requirement was significantly less (p < 0.001) with the slower infusion rate (median = 7.5 mg kg(-1); range 4.9-13.7) compared with the faster infusion rate (median =11.0 mg kg(-1); range 6.6-18.0). The quality of sedation also affected the dose required (p = 0.03). The slower infusion rate was associated with a significantly poorer induction quality (p = 0.03) [corrected] CONCLUSIONS: Slow thiopental infusion (0.1 ml kg(-1) minute(-1)) for anaesthesia induction after acepromazine/pethidine pre-anaesthetic medication reduced the induction dose requirement, although the quality of induction was inferior. CLINICAL RELEVANCE: The induction dose of thiopental was reduced with a slower administration rate and so slow administration is recommended in thiopental-sensitive animals.

Anesthesia↗
PubMed1993

Labour induction policy in hospitals of different levels of specialisation.

OBJECTIVE: To examine indications for the induction of labour and variations in the current policy of induction at different levels of obstetric specialisation and to compare the outcome of induced and spontaneous labour. DESIGN: A prospective 1 year birth cohort. SETTING: Maternity hospitals in the two northernmost administrative provinces of Finland, including one university hospital and three central hospitals, three local hospitals and five health centres. SUBJECTS: Eight thousand six hundred and six singleton pregnancies, including 1679 with induced labour. MAIN OUTCOME MEASURE: Data collection on age, parity, social factors and education at antenatal clinic. Data on labour collected from the hospital records after delivery. RESULTS: Labour was induced significantly more often at units of the lowest level of specialisation, the health centres (29.4%) than at the local hospitals (23.6%, P < 0.003) or in the most specialised central hospitals (17.7%, P < 0.0001). Cases of induced labour accumulated on working days. Indicative reasons, such as maternal or fetal conditions, comprised 45.0% of the indications for induction, the most common causes being elective reasons, e.g. timing of labour (51.3%). The risk of elective induction was 2.6 times greater at the primary care level than at the central hospitals (95% confidence limit, CL 2.0-3.2). The corresponding risk ratio for local hospitals was 1.8 (CL 1.5-2.1). The risk of caesarean section was 1.5 times greater in the elective induction group than in the spontaneous group (CL 1.1-1.9) and 2.9 times greater in the indicative induction group. The most common indication for caesarean section was dysfunctional, arrested labour, causes such as fetal asphyxia or antenatal haemorrhage were not seen in excess. CONCLUSION: The practice of induction of labour are not consistent in different hospitals. The opinions of individual practitioners and staff routines influence the induction policy nearly as much as do medical reasons. Despite the safety of induction, a liberal induction policy leads to an increase in operative deliveries creating potential risks for the mother and child and greater expense.

Adult↗
PubMed1997

Gestational age and induction of labour for prolonged pregnancy.

OBJECTIVE: To examine the length of gestation according to menstrual and ultrasound scan dates, and the rate of induction of labour in a unit with a routine induction policy for prolonged pregnancy. DESIGN: Retrospective analysis of computer files of 24,675 pregnancies delivered in a teaching hospital between 1988 and 1995, which had a record of the last menstrual period and a dating ultrasound scan. Detailed survey of 168 casenotes of consecutive inductions of labour to establish the indications given. SETTING: Teaching hospital with policies of routine mid-trimester ultrasound scan and routine induction for prolonged pregnancy at 290 to 294 days. MAIN OUTCOME MEASURES: Gestational age at delivery by menstrual history and ultrasound biometry in spontaneous and induced labours. RESULTS: The single largest category of reasons given for induction of labour was prolonged pregnancy. 'Post-term pregnancy', from the date of expected delivery as recorded in the notes, together with 'maternal request' and 'social factors', were the reasons given for induction of labour in 71.3% of cases. Menstrual dates systematically overestimated gestational age at term when compared with scan dates. After 41 weeks, this difference exceeded the confidence limits for second trimester scan dating error, suggesting that most pregnancies which are considered 'prolonged' according to menstrual dates are in fact mis-dated. The median gestational age for induced labours was 286 days by last menstrual period but only 280 days by scan, and most (71.5%) inductions done post-term (> 294 days) according to menstrual dates were not post-term if scan dates alone are used to calculate the gestational age. The average induction rate over the seven year study period was 16.6%. It was higher when there was any gestational age error in either direction (16.8%) compared with when menstrual and scan dates were in complete agreement (13.7%, OR 1.27, CI 1.09-1.47, P < 0.001). The induction rate was highest (up to 21.8%) in the cases where menstrual dates overstated gestational age without exceeding the usual limits for adjusting dates according to scan. Such overestimation within tolerance limits of 7, 10 or 14 days occurred in 37.1%, 45.8%, or 52.6% of all pregnancies, respectively. CONCLUSIONS: Most pregnancies undergoing post-term induction are not post-term when assessed by ultrasound dates. Regardless of whether prolonged pregnancy is considered to be a risk factor requiring intervention, the proportion of pregnancies considered 'post-term' can be reduced considerably by a dating policy which ignores menstrual dates and establishes the expected delivery date on the basis of ultrasound dates alone.

Cesarean Section↗
PubMed2004

Induction of labour for women with a previous Caesarean birth: a systematic review of the literature.

AIMS: To compare the benefits and harms of planned elective repeat Caesarean section with induction of labour and to assess different methods of cervical ripening and induction of labour for women with a previous Caesarean birth who require induction of labour in a subsequent pregnancy. METHODS: The Cochrane controlled trials register and MEDLINE (1966-current) were searched using the following terms: vaginal birth after C(a)esare(i)an, trial of labo(u)r, elective C(a)esare(i)an, C(a)esare(i)an repeat, induction of labo(u)r, prostaglandins, prostaglandin E(2), misoprostol, prostaglandin E(1) analogs, mifepristone, oxytocin, Syntocinon, randomis(z)ed controlled trial, randomis(z)ed trial and clinical trial, to identify all published randomised controlled trials with reported data comparing outcomes for women and infants who have a planned elective repeat Caesarean section with induction of labour; and different methods of induction of labour, where a prior birth was by Caesarean section. RESULTS: There were no randomised controlled trials identified where women with a prior Caesarean birth, whose labour required induction in a subsequent pregnancy, compared elective repeat Caesarean section with induction of labour. There were three randomised controlled trials identified in which women with a prior Caesarean section were allocated to different methods of induction of labour - vaginal prostaglandin E(2) versus intravenous oxytocin; mifepristone versus placebo; and vaginal misoprostol versus intravenous oxytocin. These studies varied considerably in the methods used and meta-analysis was not appropriate. CONCLUSIONS: There is a paucity of safety information for induction of labour agents in the women with a scarred uterus, and caution should be exercised in their use.

Cesarean Section, Repeat↗
PubMed1994

Effect of foscarnet induction treatment on quantitation of human cytomegalovirus (HCMV) DNA in peripheral blood polymorphonuclear leukocytes and aqueous humor of AIDS patients with HCMV retinitis. The Italian Foscarnet Study Group.

The aim of this study was to investigate peripheral blood polymorphonuclear leukocytes and, whenever possible, aqueous humor from 65 AIDS patients with ophthalmoscopically diagnosed human cytomegalovirus (HCMV) retinitis to determine (i) whether patients consistently carry viral DNA and (ii) to what extent foscarnet induction treatment decreases viral DNA levels. HCMV DNA was quantified by PCR using densitometric analysis of hybridization products obtained from external standards and a standard curve from which the number of genome equivalents of test samples, normalized by using an internal amplification control, was interpolated. Results showed that 56 of 65 patients (86.1%) were positive for HCMV DNA prior to induction treatment. Of 41 of the 56 patients (73.2%) whose blood had become DNA negative after induction, only 5 had a high viral load (> 5,000 genome equivalents per 2 x 10(5) polymorphonuclear leukocytes) prior to induction, whereas as many as 13 of the 15 (26.8%) patients remaining DNA positive after induction had a high viral load prior to induction. Finally, of the nine patients (13.8%) with DNA-negative blood prior to induction treatment, three were shifted to foscarnet from ganciclovir, while six were erroneously enrolled in the study. Pre- and postinduction aqueous humor samples were obtained from 12 patients; all of these were DNA positive prior to induction, whereas after induction, 4 became negative, 6 showed a marked decrease in viral DNA, and 2 had nearly stable low DNA levels. In conclusion, PCR is a valuable tool for etiologic diagnosis and monitoring of HCMV retinitis treatment in AIDS patients. HCMV DNA is consistently present in the blood and aqueous humor of all patients with HCMV retinitis. Foscarnet induction treatment is highly effective in suppressing or reducing DNA levels in both blood leukocytes and aqueous humor.

AIDS-Related Opportunistic Infections↗
PubMed1998

Interaction of tumor necrosis factor receptor-associated factor signaling proteins with the latent membrane protein 1 PXQXT motif is essential for induction of epidermal growth factor receptor expression.

The Epstein-Barr virus latent membrane protein 1 (LMP1) oncoprotein causes multiple cellular changes, including induction of epidermal growth factor receptor (EGFR) expression and activation of the NF-kappaB transcription factor. LMP1 and the cellular protein CD40, which also induces EGFR expression, interact with the tumor necrosis factor receptor-associated factor (TRAF) proteins. The LMP1 carboxy-terminal activation region 1 signaling domain interacts specifically with the TRAFs and is essential for EGFR induction through a mechanism independent of NF-kappaB alone. LMP1 and CD40 share a common TRAF binding motif, PXQXT. In this study, the PXQXT motifs in both LMP1 and CD40 were altered and mutant proteins were analyzed for induction of EGFR expression. Replacement of the T residue with A in CD40 completely blocked induction of the EGFR, while the same mutation in LMP1 did not affect EGFR induction. Replacement of both P and Q residues with A's in LMP1 reduced EGFR induction by >75%, while deletion of PXQXT blocked EGFR induction. These results genetically link EGFR induction by LMP1 to the TRAF signaling pathway. Overexpression of TRAF2 potently activates NF-kappaB, although TRAF2 did not induce expression of the EGFR either alone or in combination with TRAF1 and TRAF3. In vivo analyses of the interaction of the TRAFs with LMP1 variants mutated in the PXQXT domain indicate that high-level induction of EGFR expression requires interaction with TRAF1, -2, and -3. However, exogenous expression of TRAF3 decreased EGFR induction mediated by either LMP1 or CD40. These data suggest that TRAF-mediated activation of EGFR expression requires assembly of a complex containing the appropriate stoichiometry of TRAF proteins clustered at the cell membrane with LMP1.

Binding Sites↗
PubMed1997

Induction of LTD in the dentate gyrus in vitro is NMDA receptor independent, but dependent on Ca2+ influx via low-voltage-activated Ca2+ channels and release of Ca2+ from intracellular stores.

The mechanisms of the induction of long-term depression (LTD) of field excitatory postsynaptic potentials (EPSPs) and whole cell patch-clamped excitatory postsynaptic currents (EPSCs) were studied in the dentate gyrus of the rat hippocampus. LTD of field EPSPs measuring 40% of control at 30 min poststimulation was induced by low-frequency stimulation consisting of 900 pulses at 1 Hz. LTD of EPSCs measuring 37% of control was induced by a pairing procedure consisting of 60 pulses at 1 Hz applied under voltage clamp at a holding potential of -40 mV. The induction of LTD of field EPSPs was dependent on an influx of extracellular calcium, being reduced in a low-Ca2+ (0.8 mM) medium. However, substantial LTD (26%) was still induced in such a medium, demonstrating the relatively low sensitivity of LTD induction to the level of extracellular Ca2+. A high concentration of the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (100 microM) did not significantly inhibit the induction of LTD of EPSCs evoked by the intracellular pairing procedure. D-AP5 partially reduced the magnitude of LTD of field EPSPs, but substantial LTD was still induced in the presence of AP5. The induction of LTD was strongly inhibited by Ni2+ (50 microM) but not by nifedipine (10 microM), indicating that Ca2+ influx via T-type, but not L-type, Ca2+ channels is required for the induction of LTD. The induction of LTD was strongly inhibited by thapsigargin, an agent known to deplete intracellular Ca2+ stores. The induction of LTD, but not long-term potentiation (LTP), was also strongly inhibited by ruthenium red, an agent known to block the ryanodine receptors located on intracellular Ca2+ stores. These results demonstrate that Ca2+ release from intracellular Ca2+ stores is required for the induction of LTD, but not LTP. The results of the present experiments suggest that the induction of LTD involves the entry of Ca2+ via low-voltage-activated voltage-gated Ca2+ channels followed by release of Ca2+ from intracellular ryanodine-receptor-sensitive Ca2+ stores.

Animals↗
PubMed1997

Conditions for the induction of long-term potentiation and long-term depression by conjunctive pairing in the dentate gyrus in vitro.

Conditions for the induction of long-term potentiation and long-term depression by conjunctive pairing in the dentate gyrus in vitro. J. Neurophysiol. 78: 2569-2573, 1997. The conditions under which long-term potentiation (LTP) and long-term depression (LTD) of excitatory postsynaptic currents were induced by the conjunctive pairing-type protocol of afferent stimulation and postsynaptic depolarization were studied in the medial perforant pathway-granule cell synapse of the dentate gyrus in vitro. The conjunctive pairing of 1-Hz afferent stimulation and steady state postsynaptic depolarization to 0 mV did not induce LTP or LTD. Inhibition of LTD induction with a phosphatase inhibitor or ruthenium red resulted in induction of LTP after the conjunctive pairing. Such LTP induction was N-methyl--aspartate dependent. Conversely, inhibition of LTP induction with a kinase inhibitor resulted in LTD induction after the conjunctive pairing. Thus the failure to induce LTP or LTD with the pairing protocol involving depolarization to 0 mV membrane potential was due to simultaneous activation of intracellular processes that generate the induction of LTP and LTD. Increasing the frequency of afferent stimulation to 200 Hz, even for just eight stimuli, resulted in LTP induction. The studies show that two factors govern the induction of LTP/LTD, membrane potential and frequency of afferent stimulation, with either increased depolarization or increased afferent stimulation favoring LTP induction.

2-Amino-5-phosphonovalerate↗
PubMed1997

Safety of one method of sputum induction in asthmatic subjects.

To assess the safety of sputum induction in asthmatic subjects, we conducted a retrospective review of data from 351 sputum inductions in 78 subjects from our institution. The sputum induction protcol consisted of baseline FEV1, pretreatment with albuterol 180 micrograms, postbronchodilator spirometry 15 min later, the induction procedure itself (inhalation of 3% saline for 20 min), and postsputum induction spirometry. We found that sputum induction was usually well tolerated, although some subjects developed wheeze and dyspnea. Overall, 11 of the 78 subjects (14%) had a fall in FEV1 of > or = 20% from the postbronchodilator baseline ("excessive bronchoconstriction") during their first sputum induction (range: -20 to -69%); no subject developed refractory bronchoconstriction requiring hospitalization or emergency room treatment. Only one of the 54 subjects (1.9%) with a baseline prebronchodilator FEV1 > 80% had excessive bronchoconstriction, whereas 10 of the 24 subjects (42%) whose baseline FEV1 was < or = 80% predicted did so. The change in FEV1 during sputum induction was significantly correlated with the baseline prebronchodilator FEV1% predicted, the baseline postbronchodilator FEV1% predicted, the PC20 for methacholine, and the percentage of eosinophils in induced sputum. We conclude that 180 micrograms albuterol does not prevent excessive bronchoconstriction in all asthmatic subjects undergoing sputum induction, especially in asthmatic subjects with a low baseline FEV1. Pulmonary function should be monitored regularly during sputum induction in asthmatic subjects to monitor for excessive bronchoconstriction.

Adult↗
PubMed2001

The tolerability, safety, and success of sputum induction and combined hypertonic saline challenge in children.

Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. The aim of this study is to report the success and tolerability of sputum induction alone, and in combination with a HS bronchial provocation challenge. Sputum induction alone was performed with beta2-agonist pretreatment. In the combined challenge, no beta2-agonist pretreatment was used. A high-output ultrasonic nebulizer with valve box and tubing were used to deliver 4.5% saline in doubling time periods from 0.5 s to 4 min. Outcomes assessed were completion of the test protocol, adequacy of sputum samples, decrease in FEV1, and adverse effects during the procedure. Fifty-three children who underwent a sputum induction alone, and 182 children who underwent a combined sputum induction and bronchial provocation using HS. Sputum induction alone was well tolerated, with 98% of children completing the procedure and only 4% experiencing a significant (> 15%) fall in FEV1. An adequate sample of sputum was obtained in 92% of children. The combined challenge was completed by 90% of children. A distressing cough occurred in 13% of children and irritation of the mucosa in 1% of children. In the combined challenge an adequate sample of sputum was obtained in significantly fewer children than with sputum induction alone (70% versus 92%, p < 0.05). Sputum cellular changes reflected the shorter nebulization time with sputum induction alone. We conclude that induction of sputum using HS after pretreatment with bronchodilator is well tolerated with a high success rate in children. Combining the HS challenge with sputum induction provides additional information and is a useful means of comparing AHR and AI simultaneously, but at the expense of having a reduced success rate in obtaining an adequate sample of sputum, as well as increased side effects.

Adolescent↗
PubMed2004

Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide.

The mechanisms underlying the inhibition of long-term potentiation (LTP) induction by amyloidbeta-peptide (Abeta) were investigated in the medial perforant path of the rat and mouse dentate gyrus in vitro. Evidence is presented in this study that the Abeta-mediated inhibition of LTP induction involves activation of microglia and production of reactive oxygen and nitrogen species. In control slices, Abeta strongly inhibited induction of NMDA receptor-dependent (NMDAR-dependent) LTP, although not induction of NMDAR-independent LTP or long-term depression (LTD). The inhibition of NMDAR-dependent LTP was prevented by minocycline, an agent that prevents activation of microglia. The involvement of inducible nitric oxide synthase (iNOS) was shown by the inability of Abeta to inhibit LTP induction in iNOS knock-out mice and also by the ability of two iNOS inhibitors, aminoguanidine and 1400W, to prevent the Abeta-mediated inhibition of LTP induction. The Abeta-mediated inhibition of LTP induction also was prevented by the superoxide scavenger superoxide dismutase applied together with catalase. Evidence for involvement of superoxide in the action of Abeta on LTP induction was shown by the ability of an inhibitor of NADPH oxidase to prevent the Abeta-mediated inhibition of LTP induction. The study thus provides evidence that the Abeta-mediated inhibition of LTP induction involves an inflammatory-type reaction in which activation of microglia results in the production of nitric oxide and superoxide and thence possibly peroxynitrite, a highly reactive oxidant.

Amyloid beta-Peptides↗
PubMed2005

Rat PXR reporter-gene activity correlates with the induction of CYP3A in rat precision-cut liver slices.

Recent studies have suggested that both constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) are involved in the induction of rat liver microsomal cytochrome P-450 (CYP) 2B and 3A through a mechanism called cross-talk. In this study we intend to determine if a PXR-reporter gene assay could be used for the prediction of CYP3A and/or CYP2B induction in rats. The induction of rat CYP2B and CYP3A by nineteen structurally diverse compounds was evaluated by using rat precision-cut liver slices and a rat PXR reporter-gene system. Induction of CYP2B and CYP3A mRNAs in rat liver slices was quantified by real-time polymerase chain reaction. Rat PXR activation was measured by induction of luciferase activity in rat PXR reporter-gene system. Linear regression analysis of the fold of induction of mRNA in liver slices and the fold of luciferase activity in rat PXR reporter-gene system shows that a reasonable correlation (r2 = 0.6) exists between the CYP3A induction and the rat PXR activation. A much lower correlation was observed between CYP2B induction and the rat PXR activation (r2 = 0.1). The results from this study suggest that the PXR may play a major role in the induction of rat CYP3A, but not CYP2B. Therefore, the PXR-reporter gene assay may be useful in a high-throughput screening to predict CYP3A induction in rats.

Animals↗
PubMed2000

Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia.

BACKGROUND: The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS: The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS: Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes) during remission induction, including 4 toxic deaths (11%). In contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS: Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL.

Antineoplastic Agents, Hormonal↗
PubMed1975

Demonstration of cytoplasmic processes in Millipore filters permitting kidney tubule induction.

The presence of cytoplasmic material inside thin Millipore filters between interacting mouse metanephric mesenchyme and spinal cord was investigated using different fixation methods. The transmission of induction was studied from sections of Zenker-fixed paraffin-embedded explants. Formation of kidney tubules was taken as evidence for induction. Filters with 0.8 and 0.22 mum pores permitted induction, whereas only 6 out of 31 filters with 0.1 mum pores did so. Glutaraldehyde-fixed Epon-embedded explants were used for study of cytoplasmic penetration into filters. In thick sections, filters with large pores were seen to contain cytoplasmic material at all levels. Filters with 0.1 mum pores usually showed only shallow ingrowth, but those which had permitted passage of induction contained material at least half way from the spinal cord and shallow ingrowth from the mesenchyme. With 0.8 mum filters the ingrowths from both sides met first after 18 h of transfilter cultivation. This has previously been shown to be the minimum time needed for induction to take place in this system. In electron microscopy cytoplasmic processes were seen deep inside the 0.8 and 0.22 mum filters regularly permitting induction. In small pores such material was only preserved by certain glutaraldehyde fixatives. Diffusion studies did not reveal major differences between induction-permitting 0.22 mum filters and induction-preventing 0.1 mum filters. Thus in the kidney tubule induction system this and our previous work speak in favor of a mechanism based on close apposition of cells rather than on long-range diffusion of inductive substances or on matrix interaction.

Animals↗
PubMed2004

Can differences in labor induction rates be explained by case mix?

OBJECTIVE: To determine whether differences in case mix account for variations in labor induction rates between hospitals and whether case mix adjustment is helpful in evaluating hospital induction rates. STUDY DESIGN: Using a New York State birth certificate database, factors associated with induction of labor were entered into a logistic regression to calculate labor induction probabilities. The probabilities were used to calculate expected induction rates at each of 16 regional hospitals. Each hospital's observed and expected induction rates were compared to determine the degree of residual variation. RESULTS: Excluding women who delivered by cesarean section without labor, the regional labor induction rate was 20.8%, with a 3.9-fold difference between the highest and lowest hospital rates (P < .0001). Adjusting for risk factors explained only 12.6% of the variation in induction rates. Risk adjustment to compare labor induction rates had a minimal effect on rank ordering of rates but made clearer some hospitals' rates. CONCLUSION: Differences in case mix do not explain labor induction rate variation, but adjustment for case mix may aid in interpreting rates at individual hospitals.

Adult↗
PubMed2005

Revisiting induction chemotherapy for head and neck cancer.

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination--cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Revisiting induction chemotherapy for head and neck cancer. References and reviews.

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.

Antineoplastic Combined Chemotherapy Protocols↗