ERK-dependent IL-6 autocrine signaling mediates adaptive resistance to pan-PI3K inhibitor BKM120 in head and neck squamous cell carcinoma.

Hyperactivation of phosphatidylinositol 3-kinase (PI3K) pathway occurs frequently in head and neck squamous cell carcinoma (HNSCC). However, clinical outcomes of targeting the PI3K pathway have been underwhelming. In present study, we investigated the resistant mechanisms and potential combination therapeutic strategy to overcome adaptive resistance to PI3K inhibitor in HNSCC. Treatment of NVP-BKM120, a pan-PI3K inhibitor, led to upregulation of interleukin-6 (IL-6) and subsequent activation of either extracellular signal-regulated kinase (ERK) or signal transducers and activators of transcription 3 (STAT3), causing modest antitumor effects on the growth of HNSCC cells. Blockade of autocrine IL-6 signaling with siRNA or neutralizing antibody for IL-6 receptor (IL-6R) completely abolished NVP-BKM120-induced activation of ERK and STAT3 as well as expression of c-Myc oncogene, which resulted in enhanced sensitivity to NVP-BKM120. Moreover, when compared with a pharmacologic inhibitor or silencing of STAT3, trametinib, a MEK inhibitor, in combination with NVP-BKM120 yielded more potent anti-proliferative effects by inhibiting S phase transition, arresting cells at G0/G1 phase, and downregulating IL-6 and c-Myc expression. Furthermore, as compared with either agent alone, combination of NVP-BKM120 with trametinib or tocilizumab, a humanized anti-IL-6R antibody, significantly suppressed tumor growth in NVP-BKM120-resistant patient-derived tumor xenograft (PDTX) models, which was also confirmed in PDTX-derived cell lines. Collectively, these results suggested that IL-6/ERK signaling is closely involved in adaptive resistance of NVP-BKM120 in HNSCC cells, providing a rationale for a novel combination therapy to overcome resistance to PI3K inhibitors.

LSD1 demethylates HIF1α to inhibit hydroxylation and ubiquitin-mediated degradation in tumor angiogenesis.

Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis. LSD1 demethylates HIF1α at lysine (K) 391, which protects HIF1α against ubiquitin-mediated protein degradation. LSD1 also directly suppresses PHD2-induced HIF1α hydroxylation, which has a mutually dependent interplay with Set9-mediated HIF1α methylation. Moreover, the HIF1α acetylation that occurs in a HIF1α methylation-dependent manner is inhibited by the LSD1/NuRD complex. HIF1α stabilized by LSD1 cooperates with CBP and MTA1 to enhance vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation.

Vecuronium requirements according to the operative phase during living donor liver transplantation under desflurane anesthesia.

INTRODUCTION: The requirements of nondepolarizing neuromuscular blocking agent during liver transplantation show conflicting results. We sought to evaluate the requirements according to the operative phase and find extrahepatic factors that influence neuromuscular blocking agent requirements. METHODS: We enrolled 35 patients undergoing living donor liver transplantation. Continuous infusion of vecuronium was adjusted every 15 minutes for consistent neuromuscular blockade aimed at T1/Tc of 0.10 monitored with a neuromuscular transmission module. We compared the mean infusion dose in each phase, and investigated whether it is correlated with preoperative Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, graft-recipient weight ratio (GRWR), or time to recovery of first twitch response to train-of-four (TOF) stimulation. RESULTS: There was a significant difference between vecuronium doses during each phase (P < .001): 0.48 ± 0.16 µg/kg/min, preanhepatic; 0.38 ± 0.14 µg/kg/min, anhepatic and 0.26 ± 0.07 µg/kg/min, neohepatic phase. There was a significant positive correlation between vecuronium infusion dose in the preanhepatic phase and CTP scores (P = .006, correlation coefficient = 0.465). There was also a significant negative correlation between the time to recovery of first twitch response of TOF stimulation and vecuronium infusion dose in the preanhepatic phase (P = .001, correlation coefficient = -0.546). The infusion dose during the preanhepatic phase was not associated with the MELD score, and that of neohapatic phase not with GRWR. CONCLUSIONS: The vecuronium infusion dose requirement during the anhepatic decreased compared with that in the preanhepatic phase. It further decreased during the neohepatic phase compared with the previous phases. Vecuronium infusion dose reduction is suggested especially during the neohepatic phase for early extubation. The dose during the preanhepatic phase is suggested to be determined considering the CTP score and the time to recovery of the TOF response.

Effect of active airway warming on body core temperature during adult liver transplantation.

INTRODUCTION: Active inspired gas humidification (AH) preserves body heat and maintains normothermia intraoperatively. However, it is unclear whether AH shows comparable influences during liver transplantation (OLT), which may be affected by both large internal heat loss and external heat supply. Thus, the aim of this study was to evaluate the effect of AH compared with passive humidification (PH) on body temperature in OLT. MATERIALS AND METHODS: Thirty-four adult patients undergoing living donor OLT were randomly enrolled into two groups: those given AH using a heated humidifier (HH group, n = 17) and those using a heat-and-moisture exchanger (HME group, n = 17). Both core and skin temperatures (Tc and Ts), as well as respiratory parameters, including static/dynamic lung compliances and PaO(2), were recorded at predetermined times. RESULTS: Both Tc and Ts were consistently higher among the HH versus the HME group after 2 hours of anesthesia. Differences in Tc and Ts between the two groups increased gradually over time. The overall Tc during surgery was higher among the HH than the HME group (P = .023). The incidences of hypothermia were lower in the HH group at 3 hours of anesthesia, 1 and 3 hours of reperfusion, and at the end of surgery (P = .037, 0.024, 0.005, and 0.010 respectively). The duration of hypothermia was lower in the HH than the HME group (3.9 ± 3.5 hours versus 6.7 ± 3.3 hours, P = .025). Both groups showed no significant intraoperative changes in respiratory parameters; there were no postoperative respiratory complications. CONCLUSION: Active humidification warms the patient's body effectively, lessening the incidence and duration of hypothermia during OLT with no respiratory risks.

Complex procedural skills are retained for a minimum of 1 yr after a single high-fidelity simulation training session.

BACKGROUND: Simulation has been shown to be effective in teaching complex emergency procedural skills. However, the retention of these skills for a period of up to 1 yr has not been studied. We aimed to investigate the 6 month and 1 yr retention of the complex procedural skill of cricothyroidotomy in attending anaesthetists using a high-fidelity-simulated cannot intubate, cannot ventilate (CICV) scenario. METHODS: Thirty-eight attending anaesthetists participated individually in a high-fidelity-simulated CICV scenario (pretest) that required a cricothyroidotomy for definitive airway management. Immediately after a debriefing and structured teaching session on cricothyroidotomy insertion, subjects managed a second identical CICV scenario (post-test). Each anaesthetist was randomized to either a '6 month retention' or a '12 month retention' group. No further teaching occurred. At their respective retention times, each anaesthetist managed a third identical CICV scenario (retention post-test). Two blinded experts independently rated videos of all performances in a random order, using a specific checklist (CL) score, a global-rating scale (GRS) score, and procedural time (PT). RESULTS: Subjects from both groups improved on their cricothyroidotomy skill performances from pretest to immediate post-test and from pretest to retention post-test, irrespective of the retention interval; CL mean (sd) 8.00 (2.39) vs 8.88 (1.53), P=0.49; GRS 28.00 (7.80) vs 31.25 (5.31), P=0.25; PT 102.83 (63.81) s vs 106.88 (36.68) s, P=0.73. CONCLUSIONS: After a single simulation training session, improvements in cricothyroidotomy skills are retained for at least 1 yr. These findings suggest that high-fidelity simulation training, along with practice and feedback, can be used to maintain complex procedural skills for at least 1 yr.

Impact of separating dairy cattle excretions on ammonia emissions.

About 80% of dairy cattle N intake is excreted in urine and feces. Urinary-N is about 75% urea, whereas fecal-N is mostly organic. Urinary-N (urea) can only be volatilized when it is hydrolyzed to ammonia (NH3) in a process catalyzed by urease, which is predominantly found in feces. Minimizing contact between urine and feces may be an effective approach to reducing urea hydrolysis and subsequent NH3 emissions. Previous studies have reported 5 to 99% NH3 emissions mitigation within barns from separation of feces and urine. The objective ofthis study was to compare NH3 emissions mitigation via separation of urine and feces in postcollection storage to a conventional scrape manure handling method where urine and feces are comingled. Laboratory scale studies were conducted to evaluate NH3 emissions from simulated postcollection storag of three waste streams: (i) idealistically separated feces and urine (no contact between urine and feces), (ii) realistically separated urine and feces (limited contact of urine and feces), and (iii) conventionally scraped manure (control). From the results of these studies, NH3 losses ranking in descending order was as follows: aggregate of realistically separated waste streams (3375.9 +/- 54.8 mg), aggregate of idealistically separated urine and feces (3047.0 +/- 738.0 mg), and scrape manure (2034.0 +/- 106.5 mg), respectively. Therefore, on the basis of these results, the extra effort of separating the waste streams would not enhance mitigation of NH3 losses from postcollection storage of the separated waste streams compared to the conventional scrape manure collection system.

Patient- and operator-related factors associated with successful Glidescope intubations: a prospective observational study in 742 patients.

The Glidescope Video Laryngoscope (Glidescope, Verathon Medical, Bothell, WA, U.S.A.) is a relatively new intubating device. It has been proposed to be useful for securing both routine airways and those where direct laryngoscopy may be difficult. In this prospective observational study, data for 742 intubations using the Glidescope were collected to investigate whether four factors are associated with successful tracheal intubation at first attempt using the Glidescope: previous Glidescope experience, previous direct laryngoscopy experience, level of anaesthesia training and clinical airway assessment. The likelihood of successful tracheal intubation at first attempt using the Glidescope increased with increasing previous Glidescope experience. Similarly, success was more likely in airways that were assessed as normal compared with those where direct laryngoscopies were either predicted or known to be difficult. Subgroup analysis indicated 83% first attempt success by 'experienced' Glidescope users in patients with documented difficult direct laryngoscopies. This supports its use as an adjunct device for management of airways where direct laryngoscopies prove difficult. With regard to the level of anaesthesia training, only medical students were more likely to fail with the Glidescope. Success was not associated with previous experience in direct laryngoscopy. The lack of association with direct laryngoscopy experience and level of anaesthesia training (beyond student level) suggests that expertise with traditional airway tools is not necessary to become proficient with the Glidescope.

Probiotic potential of Staphylococcus hominis MBBL 2-9 as anti-Staphylococcus aureus agent isolated from the vaginal microbiota of a healthy woman.

AIMS: To isolate and characterize an antagonist for use as probiotic agent in the biocontrol of Staphylococcus aureus. METHODS AND RESULTS: Bacteria that exhibited antimicrobial activity against Gram-positive bacteria including Staph. aureus were isolated from 12 healthy women, with Staphylococcus hominis MBBL 2-9 showing the strongest activity. The bacteriocin produced by Staph. hominis MBBL 2-9 was purified by 60% ammonium sulfate saturation, ultrafiltration, HLB cartridge and reverse-phase HPLC. The molecular weight was estimated as 2038.2 Da by MALDI-TOF mass spectrometry. The antagonist survived up to 2 h in artificial gastric juice (pH 2.5) and grew in the presence of 1% porcine bile extract. In addition, Staph. hominis MBBL 2-9 adhered effectively to HT-29 epithelial cell line. CONCLUSION: Staphylococcus hominis MBBL 2-9 exhibited desirable probiotic traits such as acid tolerance, bile resistance and adherence to epithelial cell line. The bacterium also produced a bacteriocin with unique molecular weight and high antimicrobial activity similar to traditional antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report of a bacteriocin-producing Staph. hominis MBBL 2-9 that has potential for use as a probiotic agent against Staph. aureus.

Cognitive aid for neonatal resuscitation: a prospective single-blinded randomized controlled trial.

BACKGROUND: Retention of skills and knowledge after neonatal resuscitation courses (NRP) is known to be problematic. The use of cognitive aids is mandatory in industries such as aviation, to avoid dependence on memory when decision-making in critical situations. We aimed to prospectively investigate the effect of a cognitive aid on the performance of simulated neonatal resuscitation. METHODS: Thirty-two anaesthesia residents were recruited. The intervention group had a poster detailing the NRP algorithm and the control group did not. Video recordings of each of the performances were analysed using a previously validated checklist by a peer, an expert anaesthetist, and an expert neonatologist. RESULTS: The median (IQR) checklist score in the control group [18.2 (15.0-20.5)] was not significantly different from that in the intervention group [20.3 (18.3-21.3)] (P=0.08). When evaluated by the neonatologist, none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. A minority of the intervention group used the cognitive aid frequently. CONCLUSIONS: Retention of skills after NRP training is poor. The infrequent use of the cognitive aid may be the reason that it did not improve performance. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into the NRP training.

Measuring concentrations of ammonia in ambient air or exhaust air stream using acid traps.

Strong acid solutions have been widely used in acid traps to determine concentrations of ammonia in ambient air or exhaust air stream. A literature survey indicates the method has a long history and a wide variation in use. Through a series of studies, this paper examines several factors including volume of the acid, depth of the acid, and airflow rate; that might affect the efficiency of sulfuric acid traps and recommends steps researchers and other users may take to ensure reliable results from this method. The results from these series of studies indicate: (i) an inverse relationship between the efficiency of the acid traps and the amount of ammonia to be trapped even when the capacity of the acid trap is excessively greater than the maximum theoretical stoichiometric capacity needed to dissolve all of the ammonia, (ii) for the same volume of acid, the efficiency of the acid trap increased with the acid depth but overall, the efficiency at any given acid depth decreased as the amount of ammonia through the trap increased, and (iii) at the two airflow rates examined in this study (0.5 and 1.0 L/min) the efficiency of the acid traps decreased at similar rates as the concentration of ammonia in the sample air increased but the efficiency of the trap was significantly higher at the lower airflow rate. To obtain reliable measurements from this method, therefore, multi-point calibrations within the entire range of target measurements is recommended to provide accurate corrections of the measurements.

Oxidant and SDS-stable alkaline protease from a halo-tolerant Bacillus clausii I-52: enhanced production and simple purification.

AIMS: An investigation was carried out on the enhancement of protease production and simple purification of an oxidant and SDS-stable alkaline protease produced by Bacillus clausii I-52 of industrial significance. METHODS AND RESULTS: The supplementation with 0.4% (w/v) NaCl and 0.05% (w/v) FeSO4.7H2O in a culture medium caused an increase in the protease production. The enzyme was purified to homogeneity with overall recovery of 79% and 10-fold purification from culture supernatant using Diaion HPA75, phenyl-Sepharose and DEAE-Sepharose column chromatographies. The protease was a halo-tolerant enzyme with apparent molecular mass of 28 kDa, and the Km and kcat values for N-Succinyl-Ala-Ala-Pro-Phe-pNA at 45 degrees C and pH 11.0 were determined to be 83.9 micromol l(-1) and 238.6 s(-1) respectively. CONCLUSIONS: Bacillus clausii I-52 was identified as a halo-tolerant bacterium, and the extracellular alkaline protease produced by B. clausii I-52 also showed extreme halo-tolerance. The enzyme stability towards SDS and H2O2 could be increased by adding NaCl or propylene glycol to the enzyme solution. SIGNIFICANCE AND IMPACT OF THE STUDY: The alkaline protease secreted by B. clausii I-52 is significant from an industrial perspective because of its stability against surfactants and oxidants as well as its tolerance towards high salinity. These enzymatic properties suggest its suitable application for industrial purposes.

Effects of environmental endocrine disruptors on the sex differentiation in Korean rockfish, Sebastes schlegeli.

The effects of estradiol-17beta, methyltestosterone, tributyltin, bisphenol A and 2,4-dinitrophenol on sex differentiation were investigated in the Korean rockfish, Sebastes schlegeli. The 51 day-old fry with undifferentiated gonads were fed with food containing the chemicals at 0.05, 0.5, 5, 50 and 100 micro/g diet for 29 days. Sex ratio and gonadal abnormality after the chemical treatment were determined by histological examination of gonads. In control group, the sex ratio of fry was 1:1.3 (female:male), and more males than females appeared. The sex of fry fed with estradiol-17beta at 5, 50 and 100 micro/g diet was all females. Feminization of the fry was induced by exogenic estradiol-17beta. In the methyltestosterone group, sex ratio of fry was 1:10.2 in 0.05 micro/g diet, 1:2.4 in 0.5 micro/g diet, 1:3.1 in 5 micro/g diet, 1:1.2 in 50 micro/g diet and 1:2.3 in 100 micro/g diet. Masculinization of the fry was induced by methyltestosterone at the lowest concentration. Furthermore, intersex of the fry was observed. The number of intersex fry was 23.3, 25.0 and 35.3 at 0.5, 5 and 50 micro/g diet of methyltestosterone, respectively. Sex ratio of bisphenol A group showed no difference with that of the control. The sex of fry fed with 2,4-dinitrophenol at 5, 50 and 100 micro/g diet was all females. 2,4-dinitrophenol should be considered as a new member of endocrine disruptors. In tributyltin group, the sex ratio of fry at 100 micro/g diet of tributyltin was 5.4:1. Tributyltin induced the feminization of the fry at the highest dose. Tributyltin showed an estrogenic effect in the Korean rockfish in contrast to an androgenic effect in gastropods.

Oxidant and SDS-stable alkaline protease from Bacillus clausii I-52: production and some properties.

AIMS: An investigation was carried out on an oxidative and SDS-stable alkaline protease secreted by Bacillus clausii of industrial significance. METHODS AND RESULTS: Maximum enzyme activity was produced when the bacterium was grown in the medium containing (g l-1): soyabean meal, 15; wheat flour, 10; liquid maltose, 25; K2HPO4, 4; Na2HPO4, 1; MgSO4.7H2O, 0.1; Na2CO3, 6. The enzyme has an optimum pH of around 11 and optimum temperature of 60 degrees C. The alkaline protease showed extreme stability towards SDS and oxidizing agents, which retained its activity above 75 and 110% on treatment for 72 h with 5% SDS and 10% H2O2, respectively. Inhibition profile exhibited by phenylmethylsulphonyl fluoride suggested that the protease from B. clausii belongs to the family of serine proteases. CONCLUSIONS: Bacillus clausii produced high levels of an extracellular protease having high stability towards SDS and H2O2. SIGNIFICANCE AND IMPACT OF THE STUDY: The alkaline protease from B. clausii I-52 is significant for an industrial perspective because of its ability to function in broad pH and temperature ranges in addition to its tolerance and stability in presence of an anionic surfactant, like SDS and oxidants like peroxides and perborates. The enzymatic properties of the protease also suggest its suitable application as additive in detergent formulations.

Antibiotic selective pressure for the maintenance of antibiotic resistant genes in coliform bacteria isolated from the aquatic environment.

Coliform bacteria isolated from the aquatic environment were investigated for antibiotic susceptibility and detailed structures of class 1 integrons. A high proportion of isolates were found to be resistant to sulfamethoxazole, aminoglycosides, and beta-lactams. The 750 (53.6%) isolates were resistant to one or more of the antibiotics tested out of 1,400 coliform bacteria. Based on the MIC of antibiotics and antibiogram, 150 isolates were selected and further studied for class 1 integrons. The intI1 gene was found in 36 (24.0%) of the 150 isolates. Twelve isolates carried the gene cassettes responsible for antibiotic resistance, while no gene cassettes were found in 24 isolates. Seven different genes, dfrA5, dfrA7, dfrA12, dfrA17, aaA2, aaA5, and aad(3'), were detected in gene cassettes. The dfrA and aad genes located on class 1 integrons were responsible for resistance to trimethoprim and aminoglycosides. The remaining 24 coliform bacteria had the incomplete or non-functional class 1 integrons. These results indicated that antibiotic selective pressures may play an important role to maintain gene cassettes of class 1 integrons and in the absence of sustained antibiotic pressures, such as the aquatic environment, coliform bacteria may carry empty or non-functional class 1 integrons.

Prevalence of swine influenza virus subtypes on swine farms in the United States.

Serologic and virologic prevalence of infection with different swine influenza virus (SIV) subtypes was investigated using swine sera, nasal swabs and lung samples that had been submitted for a diagnosis to the Minnesota Veterinary Diagnostic Laboratory. A total of 111,418 pig sera were tested for SIV antibody between 1998 and 2000, and 25,348 sera (22.8%) were found to be positive by the hemagglutination inhibition (HI) test. Of the positive samples, 16,807 (66.7%) and 8,541 (33.7%) had antibody to H1 and H3 subtypes, respectively. Between January 1998 and May of 2001, a total of 3,561 nasal swabs or lung samples were examined for the presence of SIV, and SIV was isolated from 1,124 samples (31.7%). Of these isolates, 869 (77.3%) and 255 (22.7%) were subtyped as H1 and H3, respectively, by the HI method. For further characterization, 120 SIV isolates each from 1998 to 2001 were randomly selected from a culture collection and their hemagglutinin (HA) and neuraminidase genes examined by reverse transcription-PCR and sequencing. Of the 480 isolates, 322 (67.1%), 22 (4.6%) and 129 (26.9%) were subtyped as H1N1, H1N2 and H3N2, respectively. The remaining 7 samples (1.5%) were found to contain both H1N1 and H3N2 viruses. The SIV H1N2 subtype was isolated from 1, 8, and 13 samples in 1999, 2000, and 2001, respectively. The 22 H1N2 isolates originated from 9 different states of the United States. Genetic screening of the HA genes of 12 selected H1N2 isolates showed that 8 of them had a close phylogenetic relationship with the Indiana isolate of H1N2 (A/Swine/Indiana/9K035/99), while 4 isolates were closely related to classical SIV H1N1.

Detection and subtyping of swine influenza H1N1, H1N2 and H3N2 viruses in clinical samples using two multiplex RT-PCR assays.

A total of 360 type A swine influenza virus-positive samples including cell culture isolates, nasal swabs or lung tissues along with 30 virus-negative samples were tested for the detection and subtyping of H1N1, H1N2 or H3N2 by two multiplex reverse transcription (RT)-PCR assays. The positive samples had been collected between 1999 and 2001 from pigs with respiratory diseases, and type A influenza virus was isolated and subtyped by hemagglutination inhibition (HI) test at the Minnesota Veterinary Diagnostic Laboratory (MVDL). Two multiplex RT-PCR assays specific for H1 and H3, and N1 and N2 were developed. RT-PCR products with unique sizes characteristic of each subtype of influenza A virus were sequenced, and the sequences were demonstrated to be specific for H1N1, H1N2 or H3N2. Genomic RNAs or DNAs from 12 common swine pathogens other than type A influenza viruses were not amplified when the PCR assays were performed with these primer sets. Positive amplification reaction could be visualized with RNA extracted from up to 10(-5) dilution of each reference virus with original infectivity titer of 10(5) TCID(50)/ml. Of the 360 samples tested, swine influenza virus H1N1, H1N2 and H3N2 were identified in 200, 13 and 139 samples, respectively. The remaining eight samples were positive for both H1N1 and H3N2 viruses. The results of multiplex RT-PCR were 100% in agreement with those of virus isolation. These results demonstrate the usefulness of multiplex RT-PCR for detection and identification of influenza A virus subtypes. The results also indicate an increased occurrence of H1N2 in US swine population.

A comparison of patient-controlled sedation using either remifentanil or remifentanil-propofol for shock wave lithotripsy.

UNLABELLED: Patient-controlled sedation (PCS) has been used for extracorporeal shock wave lithotripsy (SWL) because it allows for rapid individualized titration of anesthetics. Because of its sedating effects, the addition of propofol to remifentanil may improve patient tolerance of SWL with PCS. One hundred twenty patients were randomly assigned to receive remifentanil 10 microg or remifentanil 10 microg plus propofol 5 mg for PCS with zero-lockout interval. Nine patients in the Remifentanil group and three patients in the Remifentanil-Propofol group required additional sedatives to complete their SWL (P = 0.128). Compared with the Remifentanil group, the Remifentanil-Propofol group required less remifentanil, had a decreased incidence of postoperative nausea and vomiting, and had a better overall satisfaction level. However, they had an increased incidence of transient apnea and oxygen desaturation. The incidence of apnea was 15% in the Remifentanil group and 52% in the Remifentanil-Propofol group (P < 0.001). All patients were able to move themselves to the stretcher at the end of SWL, and median time to home discharge was <70 min in both groups. Both remifentanil and remifentanil-propofol were useful for PCS during SWL. IMPLICATIONS: The addition of propofol to remifentanil improves patient satisfaction and decreases postoperative nausea and vomiting. However, it causes more respiratory depression than remifentanil alone. When remifentanil-propofol is used with patient-controlled sedation, appropriate monitoring and a minimum 1-2 min lockout interval is required.