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Metallothionein-IIA promoter induction alters rat intestinal fatty acid binding protein expression, fatty acid uptake, and lipid metabolism in transfected L-cells.

Mouse L-cell fibroblasts, transfected with the cDNA encoding for rat intestinal fatty acid-binding protein (I-FABP) under the control of the human metallothionein-IIA promoter, were tested for their protein inducibility by the heavy metals cadmium (Cd2+) and zinc (Zn2+). I-FABP levels were quantitated by Western immunoblotting. Expression of I-FABP in all transfected cell lines tested was induced several-fold by optimized levels of Cd2+ and Zn2+. Induction conditions had no effect on cell growth rates or cell densities for any of the cell lines. Induction of high I-FABP-expressing cells (H141) decreased the initial rate and extent of uptake of cis-parinaric acid, a nonmetabolizable fatty acid, and of [3H]oleic acid, an esterifiable fatty acid. These effects of induction were specific for I-FABP-expressing cells since they were not observed in control cells or cells expressing a high level of liver (L-) FABP. Induction of H141 cells also significantly altered the esterification and distribution of exogenous [3H]oleic acid, especially among triglycerides and phosphatidylcholine, but less so among other glycero-phospholipids, cholesteryl esters, and phosphatidylethanolamine. Induction of H141 cells normalized [3H]oleic acid esterification into cholesteryl esters, phosphatidylcholine, total neutral lipids, and total phospholipids such that they no longer differed from control levels. In contrast, induction did not normalize [3H]oleic acid esterification into triacylglycerols and phosphatidylethanolamine to control levels in H141 cells; both remained significantly increased over control cells. Therefore, promoter induction levels of Cd2+ and Zn2+ enhanced I-FABP expression in H141 cells, thereby modulating both fatty acid uptake and intracellular esterification into neutral and phospholipids.

Animals↗

CD2 regulates T cell-dependent induction of monocyte IL-1 beta mRNA during anti-CD3 mitogenesis.

The induction of monocyte IL-1 mRNA during T cell activation requires that monocytes receive contact-dependent signals from activated T cells. Furthermore, the ability of T cells to induce IL-1 beta mRNA is not constitutive but rather is rapidly acquired (< or = 30 min) following activation via mechanisms that do not require protein synthesis. The goal of these studies is to identify the T cell signal(s) that mediates the cell contact-dependent induction of monocyte IL-1 beta mRNA. The induction of IL-1 beta mRNA during anti-CD3 mitogenesis was significantly inhibited by anti-CD2 mAb, whereas mAb against CD11a, CD18, CD69, or CD5 molecules had no effect. The inhibition of IL-1 beta mRNA induction by anti-CD2 mAb was restricted to only those mAb that block CD2/CD58(LFA-3) interactions. Furthermore, anti-CD2 blocked the induction of monocyte IL-1 beta mRNA by T cells that were preactivated using either immobilized anti-CD3 or anti-T11(2) plus anti-T11(3) mAb, thereby indicating that the inhibition of IL-1 beta mRNA was not due to negative signaling effects exerted on the T cell by anti-CD2. Finally, although anti-CD69 mAb had no effect on IL-1 beta mRNA induction, it inhibited the generation of soluble IL-1 beta. The combination of anti-CD69 and anti-CD2 mAb exhibited greater inhibition of secreted IL-1 beta than either antibody alone. These results indicate that CD2 is required for T cell induction of IL-1 beta mRNA through interaction with LFA-3 on the monocyte and that the generation of soluble IL-1 beta is regulated by CD69.

Antibodies, Monoclonal↗

Induction of notochord during ascidian embryogenesis.

The tadpole larva of solitary ascidians has 40 notochord cells in its tail. Of these cells, 32 in the anterior and middle part of the tail are derived from the A-line blastomeres, while 8 in the posterior part of the tail originate from the B-line blastomeres. Previous experiments involving continuous dissociation of daughter blastomeres from the first cleavage to the 110-cell stage suggested that cellular interactions may be involved in the formation of notochord cells. In the present study, the presumptive-notochord blastomeres isolated from the 32-cell embryos did not develop features of notochord. These results suggest that cellular interactions may be required for the fate specification of notochord, that is to say, notochord formation occurs as a result of inductive interaction between blastomeres. In order to confirm the involvement of induction in the determination of notochord and to identify the inducer blastomeres, the presumptive-notochord blastomeres at the 32-cell stage were coisolated or recombined with one of the surrounding blastomeres in a series of experiments. The results suggested that, for the A-line precursors, notochord differentiation occurs as the result of an inductive influence from vegetal blastomeres that include the presumptive-endoderm blastomeres and the presumptive-notochord blastomeres themselves. It was also suggested that induction of notochord is complete by the 64-cell stage and that inductive interactions have to be initiated before the decompaction of blastomeres during the 32-cell stage. Ascidians are Urochordata and are closely related to vertebrates. In vertebrates, it is well known that inductive interactions play a crucial role in the determination of notochord. It appears, therefore, that induction of notochord is common throughout the phylum Chordata.

Alkaline Phosphatase↗

The biphasic induction of p21 and p27 in breast cancer cells by modulators of cAMP is posttranscriptionally regulated and independent of the PKA pathway.

Cyclic AMP (cAMP) elevation affects growth arrest and differentiation in a wide variety of breast cell lines; however, the mechanisms associated with this process are poorly understood. Previous studies linked cAMP-mediated growth arrest in breast tumor cells to increased levels of cyclin kinase inhibitor (CKI), p21. In the present study we examined the role of cAMP-dependent protein kinase (PKA) on p21 and p27 induction in the breast cancer cell line, MDA-MB-157. The induction of the CKIs by modulators of cAMP such as cholera toxin (CT) + 1-isobutyl-3-methylxanthine (IBMX) and lovastatin fluctuates with biphasic kinetics (although the kinetics of CKI induction with CT + IBMX treatment are different from that of lovastatin) and is depicted by the periodic accumulation of lower molecular weight forms of p21 and p27 which also correlate with fluctuations in CDK2 activity. Using three different approaches we show that the cAMP-mediated induction of CKIs is independent of PKA activity. In the first approach we treated MDA-MB-157 cells with a variety of cAMP modulators such as CT + IBMX, and forskolin in the presence or absence of H-89, a potent PKA inhibitor. This analysis revealed that the cAMP activators were capable of inducing p21 even though PKA activity was completely eliminated. In the second approach PKA dominant negative stable clones of MDA-MB-157 treated with CT + IBMX or forskolin also resulted in p21 induction, in the absence of any PKA activity. Last, treatment of MDA-MB-157 cells with lovastatin, another known cAMP modulator which also causes growth arrest, resulted in the induction of p21 and p27 without any increase in PKA activity. Collectively, the above results suggest that the induction of p21 by cAMP is through a novel pathway, independent of PKA activity.

1-Methyl-3-isobutylxanthine↗

2-Mercaptoethylamine, radioprotector, inhibits the induction of the oxidative stress-inducible (soi) gene by paraquat in Escherichia coli.

To demonstrate the superoxide radical (.O(2)(-)) -scavenging activity of 2-mercaptoethylamine (MEA), we investigated the induction of the oxidative stress-inducible (soi) gene fused lacZ gene (soi-28:: lacZ) by the use of paraquat as a source of.O(2)(-). When MEA or cysteine was added to the cultures before paraquat treatment, soi gene induction by paraquat was significantly inhibited. However, a high quantity of ascorbic acid (5 mm) inhibited soi gene induction by paraquat far less than MEA or cysteine did. The induction of soi gene induction by MEA exhibited a dose-dependent manner in the range of over 0.2 mm. The antagonistic molecules on the radioprotective action of MEA, ascorbic acid and cysteine did not counteract MEA action on the inhibition of paraquat-mediated soi gene induction. To clarify that the MEA action on the inhibition of paraquat-mediated soi gene induction may be due, in part, to.O(2)(-)-scavenging activity, we investigated the ability of MEA to inhibit the nitroblue tetrazolium (NBT) reduction mediated by.O(2)(-)generated in the xanthine oxidase/hypoxanthine system in vitro. At concentrations above 1 mm, MEA effectively inhibited the NBT reduction in a concentration-dependent fashion. Our results demonstrated that MEA has an ability to scavenge.O(2)(-), and so protects against.O(2)(-)-mediated damage.

Ascorbic Acid↗

Relative biological effectiveness of neutrons for cancer induction and other late effects: a review of radiobiological data.

The risk of secondary cancer induction after a therapeutic irradiation with conventional photon beams is well recognised and documented. However, in general, it is totally overwhelmed by the benefit of the treatment. The same is true to a large extent for the combinations of radiation and drug therapy. After fast neutron therapy, the risk of secondary cancer induction is greater than after photon therapy. This can be expected from the whole set of radiobiological data, accumulated so far, which shows systematically a greater relative biological effectiveness (RBE) for neutrons for all the biological systems which have been investigated. Furthermore, the neutron RBE increases with decreasing dose and there is extensive evidence that neutron RBE is greater for cancer induction and for other late effects relevant in radiation protection than for cell killing at high doses as used in therapy. Almost no reliable human epidemiological data are available so far, and the aim of this work is to derive the best risks estimate for cancer induction after neutron irradiation and in particular fast neutron therapy. Animal data on RBE for tumour induction are analysed. In addition, other biological effects are reviewed, such as life shortening, malignant cell transformation in vitro, chromosome aberrations, genetic effects. These effects can be related, directly or indirectly, to cancer induction to the extent that they express a "genomic" lesion. Since neutron RBE depends on the energy spectrum, the radiation quality has to be carefully specified. Therefore, the microdosimetric spectra are reported each time they are available. Lastly, since heavy-ion beam therapy is being developed at several centres worldwide, the available data on RBE at low doses are reviewed. It can be concluded from this review that the risk of induction of a secondary cancer after fast neutron therapy should not be greater than 10-20 times the risk after photon beam therapy. For heavy ions, and in particular for carbon ions, the risk estimate should be divided by a factor of about 3 due to the reduced integral dose. The risk has to be balanced against the expected improvement in cure rate when the indication for high-LET therapy has been correctly evaluated in well-selected patient groups.

Animals↗

Operative stress potentiates the inductivity of membrane associated lymphotoxin (mLT) on lymphokine activated killer (LAK) cells in vitro.

Membrane-associated lymphotoxin (mLT) is induced in human peripheral blood mononuclear cells when cultured with interleukin 2, in the form of lymphokine-activated killer (LAK) cells. The inductivity of mLT is thought to be dependent upon the differentiation potential of LAK cell precursors, being T cells and natural killer cells. In this study, we investigated the inductivity of mLT on LAK cells from surgical patients. The preoperative values of mLT inductivity were found to be generally higher in malignant than benign cases, and the postoperative time course of mLT inductivity showed a transient decrease immediately after the operation followed by gradual increase over 2 weeks. Moreover, patients with an intraoperative bleeding volume of more than 1,000 ml showed a delay in the postoperative increase of mLT inductivity. These data suggest that operative stress potentiates the inductivity of mLT on LAK cells; however, excess stress may cause a delay in the restoration of mLT inductivity.

Adult↗

Prophage induction in thermosensitive DNA mutants of Bacillus subtilis.

Incubation of thermosensitive dna mutants of Bacillus subtilis at the non-permissive temperature leads in some instances to induction of defective prophage PBSX and cell lysis. A clear distinction can be made between mutants affected in DNA replication at the growing point (extension mutants) and those unable to initiate new rounds of replication (initiation mutants). The former promote PBSX induction to a variable and mutation-specific extent, whereas the latter do not exhibit any signs of induction. Analysis of mutants carrying two dna mutations suggests that products of some dna genes involved in initiation and in extension are not essential for induction but can substantially amplify its extent. However, mitomycin C treatment of dna mutants which have completed their residual DNA synthesis leads to a PBSX induction essentially identical to that obtained by mitomycin C treatment of the wild-type strain, which precludes an essential role for any of the mutated proteins in this induction process. On the basis of our observations we propose that the induction signal is related to the number of blocked replication forks: the larger that number, the higher the proportion of induced cells within the population.

Bacillus subtilis↗

Genetic analysis of L-ethionine-mediated induction of alpha-fetoprotein in mice.

Two genetic loci regulate hepatic alpha-fetoprotein (AFP) mRNA levels in adult mice. The raf locus controls basal levels and the Rif locus determines the degree of induction during liver regeneration. We have investigated the function of each locus during L-ethionine-mediated AFP induction using adult female mice with different Rif/raf genotypes. A single intraperitoneal injection of L-ethionine (0.5 mg/g body weight) resulted in significant triglyceride accumulation in hepatic parenchymal cells and increased AFP synthesis 48-96 h following injection. Hepatic AFP mRNA levels in Balb/cJ mice (high basal level/high induction level during regeneration) were 10- to 30-fold higher than Balb/cCRBL or C3H/He mice (low basal level/high induction level) following ethionine injection, indicating that raf-mediated differences persisted throughout the course of acute ethionine poisoning. The magnitude of this induction was similar to that seen during carbon tetrachloride-induced regeneration. In contrast, C57BL/6 mice (low basal level/low induction level during regeneration) contained hepatic AFP mRNA levels similar to Balb/cCRBL and C3H/He mice following ethionine injection. Thus, Rif-dependent differences seen during liver regeneration were not seen during acute ethionine poisoning. This leads us to conclude that (1) hepatic AFP mRNA induction by ethionine may not be mediated by the Rif locus if Rif is a transcriptional inducer, or (2) if Rif is a transcriptional repressor, it is inactivated equally in all strains during acute ethionine poisoning, unlike during liver regeneration. Hepatic albumin mRNA levels were not affected by ethionine treatment in vivo. L-Ethionine elevated AFP mRNA levels in primary mouse hepatocyte cultures; however, ethionine treatment also increased albumin mRNA levels in vitro.

Albumins↗

Influence of serum protein, serum albumin concentrations and dose on midazolam anaesthesia induction times.

Individual variation occurs in time to induction of anaesthesia with intravenous drugs. Less free drug is available to cross the blood-brain barrier when the drug is highly protein bound. Since this may prolong time to sleep, we correlated the induction time, serum albumin and total protein concentrations, and doses of midazolam, which is a highly protein bound intravenous anaesthetic. There is a poor correlation (r = 0.062) between induction time and serum protein, a weak (r = 0.542) but statistically significant (p = 0.026) correlation between induction time and serum albumin, and a highly significant (p = 0.003) negative correlation (r = 0.579) between drug dose and induction time. The administration of the appropriate dose of midazolam for induction, therefore, appears to affect induction time more significantly than does the serum albumin concentration.

Anesthesia, Intravenous↗

Rapid inhalational induction of anaesthesia with isoflurane or halothane in humidified oxygen.

This study was designed to determine the relative speeds of induction and complication rates using either halothane or isoflurane for rapid inhalational induction of anaesthesia. Forty ASA physical status 1 and 2, unpremedicated patients presenting for day-care dental surgery received a rapid inhalational induction (RII) with either halothane 3.5% or isoflurane 5% in humidified oxygen. The carrier gas was humidified in order to limit airway irritation caused by the pungency of the volatile agents. Isoflurane produced a faster induction than halothane-121(50) (SD) sec vs 176(36) sec (P less than 0.01). Complication rates during induction (coughing, secretions, excessive movement and abandoned inductions) were similar for the two groups. The majority of patients in both the isoflurane group (17/20) and the halothane group (14/20) found the technique of RII to be acceptable. The incidences of headache, nausea and vomiting were low and not significantly different for the two groups. Isoflurane 5% in humidified oxygen is as acceptable for RII as halothane 3.5% and has a similar complication rate. Isoflurane may be used for RII in cases where it is deemed necessary to avoid halothane, or when a more rapid inhalational induction is required than is possible with halothane. The technique of RII with either agent in unpremedicated patients is well suited to day-care anesthesia.

Adult↗

Vital capacity rapid inhalation induction technique: comparison of sevoflurane and halothane.

Induction of anaesthesia using the vital capacity rapid inhalation induction (VCRII) technique with either sevoflurane or halothane was compared. The induction time, characteristics, and acceptability were assessed. Thirty-two volunteers were given one of the vapours: 17 received sevoflurane and 15 halothane. Subjects were unpremedicated and breathed approximately 2.6 x minimum alveolar concentration (MAC) equivalent of either agent. There were no differences in the patients' cardiovascular or respiratory variables. The mean time for induction of anaesthesia with halothane (153 +/- 46 sec, SD) was slower than with sevoflurane (81 +/- 22 sec, SD, P < 0.05), reflecting its higher blood:gas solubility. There were fewer induction complications such as coughing and movement in the sevoflurane than in the halothane group. Subjects in the sevoflurane group found the smell of anaesthetic more acceptable than those in the halothane group (65% vs 13%, respectively). Subjects in both groups had no objection to undergoing the procedure again. It is concluded that both halothane and sevoflurane are effective in VCRII of anaesthesia without premedication. However, the slower speed of induction with halothane frustrated the anaesthetist because of the longer induction time, and may increase the chance of pronounced excitatory phenomena occurring.

Adult↗

Parental upset associated with participation in induction of anaesthesia in children.

To evaluate the magnitude of parental upset associated with (1) the features of induction most upsetting to parents; (2) the characteristics of parents most likely to become upset; and (3) the accuracy of the anaesthetist's perception of the magnitude of parental upset. The parents (101 mothers and 43 fathers) of 103 children scheduled for elective outpatient surgery requiring general anaesthesia with induction by mask were asked on admission to participate in this study. Parents and children were educated about anaesthesia and surgery according to unit protocols. Immediately after induction of anaesthesia, the parents were asked to complete a demographic information sheet and the Parental Reactions to Anesthesia Induction Questionnaire. Responses were analyzed using descriptive statistics and content analysis. The most upsetting factors for both mothers and fathers in order of significance were: (1) separation from the child after induction of anaesthesia; (2) watching/feeling the child go limp during induction; and (3) seeing the child upset before induction. Characteristics of parents most likely to become upset revealed positive correlations between the amount of upset between mothers and fathers, mothers of an only child, and mothers or fathers who were health care workers (P < 0.05). The anaesthetist's perception of upset correlated with maternal (P < 0.05), but not parental, self-assessment of upset. We conclude that selected factors of parental participation are upsetting for the parents and that recognizing the factors associated with parental upset may enable operating room personnel to minimize these negative consequences.

Anesthesia↗

Effects of anesthetic induction on myocardial function and metabolism: a comparison of fentanyl, sufentanil and alfentanil.

Anaesthetic induction may induce myocardial ischaemia. A prospective randomized trial was instituted to compare the effect on ventricular function and myocardial metabolism of induction with fentanyl (FEN) or its analogues sufentanil (SUF) or alfentanil (ALF) in 96 patients undergoing elective coronary artery bypass grafting (CABG). Haemodynamic, metabolic (coronary sinus oxygen and lactate extraction) and gated ventriculographic measurements were made awake pre-induction (PRE), after induction (IND) and after intubation (INT). Induction was performed with FEN 75 micrograms.kg-1, SUF 15 micrograms.kg-1 or ALF 125 micrograms.kg-1 and metocurine. Fentanyl induction was associated with the greatest stability of mean arterial pressure (MAP), cardiac performance, and systolic function without associated myocardial lactate production. SUF produced the greatest depression of systolic function (p less than 0.05) but without haemodynamic instability or myocardial lactate production in all but one patient. Induction with ALF produced the greatest reduction in MAP (p less than 0.05) associated with the greatest decrease in diastolic compliance (p less than 0.05) and 50 per cent incidence of myocardial lactate production (p less than 0.05) with no significant change in coronary blood flow or myocardial oxygen consumption.

Alfentanil↗

Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.

PURPOSE: To compare the hemodynamic effects of sevoflurane when used for induction and maintenance of anesthesia with a total intravenous technique in patients with known coronary artery disease (CAD). METHODS: Thirty patients undergoing elective coronary artery bypass graft (CABG) were randomly allocated to receive either sevoflurane (S group, n = 15) at a minimal concentration of 4% in oxygen for induction and at 0.5-2 MAC end-tidal concentration for maintenance, or a total intravenous technique (T group, n = 15) consisting of midazolam for induction and propofol for maintenance. In both groups, anesthesia was supplemented with sufentanil and muscle relaxation with cis-atracurium. Hemodynamic measurements included systemic and pulmonary pressures, heart rate, mixed venous oxygen saturation and cardiac output at the following times: pre-induction, 7 and 25 min post-induction, chest closure, one hour after surgery and pre and post tracheal extubation. RESULTS: More patients in the S group (8/15) presented bradycardia in the induction period (T:2/15) (P = 0.05). During maintenance of anesthesia, treatment of hypertension was more frequent in the T group (12/15) than in the S group (6/15) (P = 0.025). All other parameters were comparable. CONCLUSION: Induction of anesthesia in patients with CAD, VCRII with sevoflurane supplemented by sufentanil provided hemodynamic responses comparable with those of TIVA although bradycardia was observed more often with sevoflurane. Intraoperative control of systemic blood pressure was achieved with fewer interventions with a sevoflurane/sufentanil maintenance than with a propofol/sufentanil technique in CABG surgery.

Aged↗

Dose-response to anaesthetic induction with sufentanil: haemodynamic and electroencephalographic effects.

PURPOSE: To determine the effect of a five-fold variation in sufentanil dose on the haemodynamic and electroencephalo graphic (EEG) response to anaesthetic induction and tracheal intubation. METHODS: Thirty-four patients undergoing elective coronary artery bypass grafting (CABG) participated in this randomized double-blind study. Patients in Group L (n = 17) received 3 micrograms.kg-1 sufentanil and those in Group H (n = 17) 15 micrograms.kg-1. Premedication was 60 micrograms.kg-1 lorazepam po. Anaesthesia and neuromuscular blockade were induced by infusing sufentanil and 0.15 mg.kg-1 vecuronium i.v. over five minutes. Haemodynamic data and the electroencephalographic (EEG) spectral edge were acquired by computer and compared at Control, Induction and Intubation. RESULTS: Sufentanil dose did not affect the haemodynamic or EEG response at end-induction. No bradyarrhythmias occurred, and the incidence of hypotension was 12% in both groups. However, during induction apparent electromyographic artifacts and a transiently greater increase in heart rate were observed in Group H. The serum sufentanil concentration at Induction was 6.1 +/- 1.8 ng.ml-1 in Group L and 25.4 +/- 8.8 ng.ml-1 in Group H, and did not correlate with haemodynamic changes. No patient recalled any intraoperative event. CONCLUSION: Increasing sufentanil dose from 3 to 15 micrograms-1 does not influence the ultimate haemodynamic response to induction. Combined with lorazepam premedication, 3 micrograms-1 sufentanil produces near-maximal haemodynamic and EEG effects and is adequate for induction and tracheal intubation of patients undergoing CABG. Sufentanil 15 micrograms.kg-1 is no more efficacious, and causes transient cardiovascular stimulation.

Aged↗

Vital capacity and patient controlled sevoflurane inhalation result in similar induction characteristics.

PURPOSE: To compare patient controlled inhalational induction (PCI) with the most commonly used sevoflurane induction technique, vital capacity inhalational induction (VCI). METHODS: Following approval of the Research Ethics Board, 124 outpatients undergoing knee arthroscopy were randomly assigned to receive either PCI or VCI sevoflurane followed by laryngeal mask airway (LMA) insertion and sevoflurane maintenance. In the PCI group, the circle circuit was not primed. The patients were asked to hold the facemask themselves and breathe normally with sevoflurane 8% in oxygen at a flow rate of 4 L x min(-1). In the VCI group, the circle circuit was primed and patients were asked to take vital capacity breaths with sevoflurane 8% at an oxygen flow rate of 8 L x min(-1). The LMA was inserted as soon as the patient's jaw was relaxed. Time from induction to LMA insertion was recorded and insertion conditions rated. The amount of sevoflurane used for LMA insertion was calculated. Vital signs were monitored at one-minute intervals until ten minutes after LMA insertion. RESULTS: Demographic data were comparable. There were no differences with respect to LMA insertion time (PCI - 3.4 min vs VCI - 3.3 min), laryngospasm (PCI - 7% vs VCI - 5%), mean arterial pressure, heart rate, SaO(2) as well as patient's overall satisfaction. CONCLUSION: PCI was comparable to VCI in sevoflurane induction with respect to the speed of induction, side effects during induction and patient satisfaction. However, PCI requires no special training and is widely applicable to all patient populations.

Adult↗

Improving results in solitary pancreas transplantation with portal-enteric drainage, thymoglobin induction, and tacrolimus/mycophenolate mofetil-based immunosuppression.

Advances in surgical techniques and clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). The purpose of this study was to analyze retrospectively the outcomes in patients undergoing solitary PTX with portal-enteric (P-E) drainage and contemporary immunosuppression. From June 1998 through December 2000, we performed 28 solitary PTXs with antibody induction and tacrolimus/mycophenolate mofetil maintenance therapy. The first 13 patients received daclizumab (DAC) induction, while the next 15 received thymoglobulin (rabbit anti-human thymocyte gamma globulin; Thymo) induction. The study group included 13 pancreas alone (PA) and 15 sequential pancreas-after-kidney-transplantations (PAKT). Solitary PTX was performed with P-E drainage in 18 patients and systemic-enteric (S-E) drainage in ten. Patient and pancreas graft survival rates were 96% and 79%, respectively, with a mean follow-up of 22 (range 1-39) months. The 1-year actual death-censored pancreas graft survival rate was 89%. One PAKT patient died with a functioning graft at 1 month; three patients (11%) experienced early graft loss due to thrombosis and were excluded from the immunological analysis, leaving 24 evaluable patients. The incidence of acute rejection was 54%, including 50% in PA and 58% in PAKT recipients ( P=NS). In patients receiving Thymo induction, the rate of acute rejection was slightly lower (43% Thymo vs 70% DAC). Moreover, P-E drainage was associated with a slightly lower rate of acute rejection (44% P-E vs 75% S-E; P=NS). In patients with both Thymo induction and P-E drainage ( n=11), there was a tendency toward less rejection (the incidence of acute rejection was 36%). Two immunological graft losses occurred (one due to non-compliance), both in patients with P-E drainage. Only one patient had a cytomegalovirus (CMV) infection. Event-free survival (no rejection, graft loss, or death) was slightly higher in patients receiving Thymo (47%) than in those on DAC (23%) induction ( P=NS). We can conclude that solitary PTX with P-E drainage and Thymo induction may be associated with improved intermediate-term outcomes and a possible immunological advantage.

Adult↗