Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group.

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.

Monte Carlo simulation and linear stability analysis of Turing pattern formation in reaction-subdiffusion systems.

Subdiffusion is an important physical phenomenon observed in many systems. However, numerical techniques to study it, especially when coupled to reactions, are lacking. In this paper, we develop an efficient Monte Carlo algorithm based on the Gillespie algorithm and the continuous-time random walk to simulate reaction-subdiffusion systems. Using this algorithm, we investigate Turing pattern formation in the Schnakenberg model with subdiffusion. First, we show that, as the system becomes more subdiffusive, the homogeneous state becomes more difficult to destablize and Turing patterns form less easily. Second, we show that, as the number of particles in the system decreases, the magnitude of fluctuations increases and again the Turing patterns form less easily. Third, we show that, as the system becomes more subdiffusive, the ratio between the two diffusive constants must be higher in order to observe Turing patterns. Finally, we also carry out linear stability analysis to validate the results obtained from our algorithm.

Analgesic efficacy of pre-operative etoricoxib for termination of pregnancy in an ambulatory centre.

INTRODUCTION: Etoricoxib is a second generation cyclooxygenase-2 inhibitor with a rapid-onset time and a long duration of action. It is ideal for providing pre-emptive analgesia for ambulatory surgeries. We hypothesised that pre-operative etoricoxib can decrease the use of fentanyl post-operatively, when compared with placebo in patients undergoing termination of pregnancy. We also compared their pain scores, time to discharge, side effects and satisfaction with analgesia post-operatively. METHODS: After approval by the hospital research ethics committee and receipt of informed written consent, we recruited 40 American Society of Anesthesiologists Physical Status Classification I and II patients scheduled for elective first trimester termination of pregnancy. Patients were randomly allocated to receive either oral etoricoxib 120 mg (Group E, n=20) or placebo tablet (Group P, n=20) pre-operatively. A blinded observer evaluated the post-operative pain scores, need for supplementary analgesia, side effects and satisfaction scores. Sample size was calculated (power of 0.8 and alpha=0.05) to detect a 20 percent difference in fentanyl usage. Amount of fentanyl used, pain scores and satisfaction scores were analysed using non-parametric tests. The incidence of side effects was analysed using chi-squared test. RESULTS: Etoricoxib 120 mg significantly decreased the amount of fentanyl required after termination of pregnancy compared to placebo (0 microg/patient, interquartile range [IQR] 0-25 versus 50 microg/patient, IQR 0-50, p-value is less than 0.05). Patients who received etoricoxib 120 mg also had significantly lower pain scores than the placebo group at time of discharge (8 +/- 11 versus 1 +/- 3, p-value is less than 0.05) and at six hours post operation (8 +/- 12 versus 0 +/- 0, p-value is less than 0.01). There was no difference in their side effects, and time to discharge and overall satisfaction were similar in both groups. CONCLUSION: Pre-operative administration of oral etoricoxib 120 mg decreased the use of fentanyl and pain scores after minor gynaecological surgery without significant side effects.

Multimodal antiemetic therapy and emetic risk profiling.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common problem with no simple solution. This review highlights factors that are known to increase the risk of PONV. It examines the various data on pharmacological and non-pharmacological methods that have been used to prevent PONV. METHODS: Peer-reviewed journals on the subject were covered. CONCLUSION: Patient, surgical and anaesthetic factors increase the risk of PONV. While patient and surgical factors are understandably difficult to control, a multimodal approach involving both pharmacological and non-pharmacological interventions has been successfully adopted to reduce the incidence of PONV. Various factors have been identified to categorise patients into different profiles to determine their risk of PONV. Perioperative strategies can then be targeted at these patient groups.

Analgesic efficacy of continuous delivery of bupivacaine by an elastomeric balloon infusor after abdominal hysterectomy: a prospective randomised controlled trial.

OBJECTIVE: To investigate the analgesic efficacy and morphine-sparing effect of continuous bupivacaine wound infiltration after abdominal hysterectomy. DESIGN: Prospective, randomised controlled trial. SAMPLE: Fifty-two female ASA I or II patients were enrolled with 26 patients in each of the study and control groups. METHODS: The study group received 0.5% bupivacaine infusion into the incisional (Pfannenstiel) wound via an elastomeric infusor at 2 mL/hr for 48 hours postoperatively plus morphine via a patient controlled analgesia (PCA) pump. The control group had only PCA morphine. RESULTS: There were no significant differences in the visual analogue scores (VAS) for pain nor PCA morphine usage for 48 hours postoperatively CONCLUSION: That continuous infusion of the incisional wound with 0.5% bupivacaine did not confer additional analgesia over PCA morphine after abdominal hysterectomy

Postoperative epidural hematoma or cerebrovascular accident? A dilemma in differential diagnosis.

An elderly lady developed an epidural hematoma following combined spinal-epidural anesthesia with a local anesthetic-opioid mixture for a vaginal hysterectomy. This occurred in association with the use of prophylactic subcutaneously administered unfractionated heparin. She had diabetes, hypertension and had previously undergone coronary artery bypass surgery and right carotid endarterectomy. Warfarin and aspirin were discontinued 2 weeks before the surgery. Postoperatively, an atypical presentation of backache, bilateral sensory loss and left lower limb monoplegia ensued. The initial clinical impression was of a cerebrovascular accident. Magnetic resonance imaging, however, revealed an extensive epidural hematoma that necessitated decompression laminectomy. Progression to paraparesis occurred but the patient gradually regained much of her functionality over the next 2 years.

Obstetric admissions to the intensive therapy unit of a tertiary care institution.

INTRODUCTION: Between 0.1% and 0.9% of women develop pregnancy complications which require admission to an intensive therapy unit. The aim of this study was to review all obstetric admissions to the intensive therapy unit at the KK Women's and Children's Hospital from 1998 to 1999 with respect to indications for admission, interventions employed and clinical outcome. METHOD: The medical records of all obstetric patients admitted to the intensive therapy unit during the 2-year period were analysed retrospectively. Subjects were included if they were admitted during pregnancy up to 42 days postpartum. RESULTS: There were 31,725 deliveries in our hospital during the study period of which there were 239 admissions to the intensive therapy unit. Of these, 42% were Malays, 41% Chinese, 12% Indians and 5% other races. 65% stayed 1 day, 24% 2 days, 7% 3 days and 4% more than 3 days. The patients' ages ranged from 18 to 44 years. The indications for admission were hypertension (50%), haemorrhage (24%), respiratory insufficiency (10%), neurological problems (11%) and sepsis (3%). Intervention-wise, 43% of patients required vasoactive infusions, 35% had arterial line placement, 22% central venous pressure monitoring, 21% ventilatory support and 2% pulmonary artery catheter placement. The maternal mortality and stillbirth rates were 1.3% and 3.7% of intensive therapy unit admissions, respectively. CONCLUSION: The admission rate to the intensive therapy unit in our institution was 0.73% of all deliveries during the 2-year study period. Hypertensive disease and haemorrhage were the predominant admitting diagnoses.

Pulse dye densitometry: a novel bedside monitor of circulating blood volume.

INTRODUCTION: Monitoring of circulating blood volume is important in the management of critically ill patients. Current methods of circulating blood volume measurements such as indicator dilution using radioisotopes or Evans blue dye are unsuitable for clinical application as these tests do not allow for frequent repeated measurements to be done. A direct bedside measurement of circulating blood volume using the principle of pulse dye densitometry was recently introduced. This is essentially an indicator dilution technique using indocyanine green combined with the principle of pulse spectrophotometry. METHODS: This paper aims to review this method of circulating blood volume measurement and provide a summary of the published clinical trials that compared its accuracy with the other conventional methods of circulating blood volume measurement, based on a Medline search, spanning the period 1966 to August 2000. RESULTS: Published studies show that pulse dye densitometry gives comparable results when compared to other conventional methods of blood volume measurement. Its ability to measure circulating blood volume accurately and repeatedly, as frequently as every 20 min makes it suitable for clinical application. CONCLUSION: Pulse dye densitometry provides for a rapid, semi-noninvasive and convenient bedside assessment of circulating blood volume that is applicable clinically. Further studies are needed to ascertain the impact of the use of pulse dye densitometry on the mortality and morbidity of the critically ill.

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia.

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.

The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.

UNLABELLED: Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for "rescue" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy. IMPLICATIONS: Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.

The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery.

We compared esmolol and remifentanil infusions with respect to their effect on intraoperative hemodynamic stability and early recovery after outpatient laparoscopic surgery when administered as IV adjuvants during desflurane anesthesia. After premedication with midazolam 2 mg IV, anesthesia was induced with propofol 2 mg. kg(-1) IV in combination with either esmolol 1 mg. kg(-1) IV (n = 27) or remifentanil 1 microg. kg(-1) IV (n = 26) and succinylcholine 1 mg. kg(-1) IV according to a randomized, double-blinded protocol. Anesthesia was initially maintained with desflurane 2.5% (subsequently titrated to maintain an electroencephalogram-bispectral index value of 60) and nitrous oxide 65% in oxygen. Before skin incision, an infusion of either esmolol (5 microg. kg(-1). min(-1)) or remifentanil (0.05 microg. kg(-1). min(-1)) was started and titrated to maintain the heart rate within 25% of the baseline value. Mivacurium, 0.04 mg/kg IV, bolus doses were administered to maintain a stable peak inspiratory pressure. Esmolol (12.8 +/- 13.1 microg. kg(-1). min(-1)) and remifentanil (0.04 +/- 0.02 microg. kg(-1). min(-1)) infusions were equally effective in maintaining a stable heart rate during these laparoscopic procedures. Although the mivacurium requirement was larger in the Esmolol group (7 +/- 5 vs 3 +/- 4 mg), the Esmolol group reported a smaller incidence of postoperative nausea and vomiting (4% vs 35%). Both drugs were associated with frequent "postanesthesia care unit bypass" rates (78-81%), short times to "home readiness" (119-120 min), excellent patient satisfaction (81-85%), and rapid resumption of normal activities (2.6-3.2 d). Fast-tracked patients were ready for discharge home significantly earlier (112 +/- 46 vs 151 +/- 50 min). We concluded that esmolol infusion is an acceptable alternative to remifentanil infusion for maintaining hemodynamic stability during desflurane-based fast-track anesthesia for outpatient gynecologic laparoscopic surgery.

Electroanalgesia: its role in acute and chronic pain management.

Interest in nonpharmacologic alternatives to conventional analgesic drugs for the management of acute and chronic pain has lead to an evaluation of the use of electroanalgesic therapies.

Comparison of the costs and recovery profiles of three anesthetic techniques for ambulatory anorectal surgery.

BACKGROUND: Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting. METHODS: Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision. RESULTS: The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%). CONCLUSIONS: The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.

Onset/offset characteristics and intubating conditions of rapacuronium: a comparison with rocuronium.

We compared onset and offset of action and tracheal intubating conditions after rapacuronium and rocuronium in 60 patients in a randomized, assessor-blinded study. Following induction of anaesthesia with propofol 2.5 mg kg-1, either rapacuronium 1.5 mg kg-1 (n = 30) or rocuronium 0.6 mg kg-1 (n = 30) was administered to facilitate tracheal intubation. Anaesthesia was maintained with either a propofol infusion (100 micrograms kg-1 min-1) or sevoflurane (1% end-tidal) with 66% nitrous oxide (N2O), n = 15 in each subgroup. Neuromuscular monitoring was performed using an electromyographic (EMG) device (Datex Relaxograph). The lag times (mean 42 (SD 11) s and 44 (16) s), maximum block (99 (2)% and 98 (3)%) and intubating conditions at 60 s (good-to-excellent in 86% and 84% of patients) were similar for rapacuronium and rocuronium, respectively. The onset time of rapacuronium was shorter than rocuronium (87 (20) vs 141 (65) s, P < 0.001), and the degree of block at 60 s was greater (69 (26) vs 50 (27)%, P < 0.05). Twenty-five per cent recovery was shorter with rapacuronium than rocuronium during propofol (15.0 (3.2) vs 39.1 (14.2) min, P < 0.001) and sevoflurane (15.1 (4.2) vs 47.8 (19.0) min, P < 0.001) anaesthesia. We conclude that rapacuronium 1.5 mg kg-1 had a more rapid onset, similar intubating conditions, and shorter recovery times than rocuronium 0.6 mg kg-1.

Rapacuronium recovery characteristics and infusion requirements during inhalation versus propofol-based anaesthesia.

We examined the effect of four maintenance anaesthetics on the neuromuscular blocking activity and spontaneous recovery characteristics after a short-term infusion of rapacuronium. Eighty ASA I-III adult patients undergoing elective surgery were studied at four centres. Anaesthesia was induced with propofol 1.5-2.5 mg kg-1 and fentanyl 1-2 micrograms kg-1, followed by a bolus of rapacuronium 1.5 mg kg-1. The patients were randomized to receive either desflurane (2-4% end-tidal, ET), sevoflurane (0.75-1.5% ET), isoflurane (0.4-0.8% ET), or a propofol infusion (75-150 micrograms kg-1 min-1) for maintenance of anaesthesia in combination with nitrous oxide (60-70%) in oxygen. When the first twitch (T1) of a train-of-four stimulus (using the TOF Guard accelerometer) returned to 5%, an infusion of rapacuronium was started at 3 mg kg-1 h-1 and adjusted to maintain T1/T0 at 10%. The duration of infusion lasted between 45 and 60 min, and the average infusion rates of rapacuronium were similar in all groups, ranging from 1.6 to 2.5 mg kg-1 h-1. There were no significant differences among the groups in the times for T1/T0 to return to 25%, 75% or 90%, or for T4/T1 to return to 70% and 80% upon discontinuation of the infusion. When potent inhalation anaesthetics are used in clinically relevant concentrations for maintenance of anaesthesia, the neuromuscular recovery profile of rapacuronium administered as a variable-rate infusion for up to 1 h is similar to that found with a propofol-based anaesthetic technique.

Fast-tracking after immersion lithotripsy: general anesthesia versus monitored anesthesia care.

UNLABELLED: Both monitored anesthesia care (MAC) and general anesthesia (GA) offer advantages over epidural anesthesia for immersion lithotripsy. We compared propofol-based MAC and desflurane-based GA techniques for outpatient lithotripsy. After receiving midazolam 2 mg IV, 100 subjects were randomly assigned to one of two anesthetic treatment groups. In the MAC group, propofol 50-100 microg. kg(-1). min(-1) IV was titrated to maintain an observer's assessment of alertness/sedation score of 2-3 (5 = awake/alert to 1 = asleep). Remifentanil 0.05 microg.kg(-1). min(-1) IV supplemented with 0.125 microg/kg IV boluses, was administered for pain control. In the GA group, anesthesia was induced with propofol 1.5 mg/kg IV and remifentanil 0.125 microg/kg IV and maintained with desflurane (2%-4% inspired) and nitrous oxide (60%). Tachypnea (respiratory rate >20 breaths/min) was treated with remifentanil 0.125 microg/kg IV boluses. In the GA group, droperidol (0.625 mg IV) was administered as a prophylactic antiemetic. Recovery times and postoperative side effects were assessed up to 24 h after the procedure. Compared with MAC, the use of GA reduced the opioid requirement and decreased movements and episodes of desaturation (<90%) during the procedure. Although the GA group took longer to return to an observer's assessment of alertness/sedation score of 5, discharge times were similar in both groups. We conclude that GA can provide better conditions for outpatient immersion lithotripsy than MAC sedation without delaying discharge. IMPLICATIONS: A desflurane-based general anesthetic technique using the cuffed oropharyngeal airway device was found to be a highly acceptable alternative to propofol-based monitored anesthesia care sedation for outpatient immersion lithotripsy.

Fibre-optic aided bougie (FAB) for simulated difficult tracheal intubation.

INTRODUCTION: Difficult intubation remains a key problem and the value of the gum elastic bougie as a first approach is well recognised. MATERIALS AND METHODS: A fine fibre-optic endoscope (Rapiscope, Cook Critical Care) was used in 50 patients to verify placement of a custom-designed hollow plastic bougie prior to "rail-roading" a tracheal tube. Following induction and muscle relaxation, direct laryngoscopy was performed after two-minutes of assisted ventilation. The laryngoscope blade was lowered to simulate difficult intubation and the bougie passed behind the epiglottis. The position of the introducer bougie was then checked using the Rapiscope. Following correct bronchoscopic identification of the tracheobronchial anatomy, a tracheal tube was then "rail-roaded" following withdrawal of the scope. RESULTS: All patients were successfully intubated following identification of the bronchial tree by the Rapiscope: three on the second attempt and the rest on the first. Mean (SD, range) time to successful bronchoscopic confirmation of correct placement of the bougie was 38 s (9.1 s, 19 to 60 s). All bronchoscopic assisted intubation were subsequently confirmed by capnography after tracheal tube insertion. Mean (SD, range) time to successful intubation was 106 s (14 s, 52 to 132 s). CONCLUSION: The fibre-optic assisted bougie (FAB) offers a promising technique in patients who may be difficult to intubate but who can be ventilated. Further developments are required to achieve a faster intubation time but oxygenation may be achieved by jetting down the hollow bougie.

Reversal of rapacuronium block during propofol versus sevoflurane anesthesia.

UNLABELLED: We studied the antagonism of rapacuronium with edrophonium-atropine during propofol- or sevoflurane- based anesthesia in 60 healthy outpatients. After the induction of anesthesia with standardized doses of propofol and fentanyl, rapacuronium 1.5 mg/kg was administered to facilitate tracheal intubation. Patients were randomized to receive either a propofol infusion (100 microg. kg(-1). min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular block was monitored by using electromyography at the wrist and reversed with edrophonium 1.0 mg/kg and atropine 0.015 mg/kg when the first twitch (T(1)) response of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. The clinical duration of action (i.e., time to 25% T(1) recovery) was similar during both propofol (13.1 +/- 3.6 min) and sevoflu-rane (13.7 +/- 4.4 min) anesthesia. The time from 25% T(1) recovery to TOF ratio of 0.8 was also similar with propofol (3.4 +/- 2.1 min) and sevoflurane (5.9 +/- 8.7 min) (P > 0.05). Although none of the patients in the propofol group required more than 9 min to achieve a TOF ratio of 0. 8, two patients receiving sevoflurane required 31 min and 37 min. Adequate antagonism of rapacuronium block with edrophonium can be achieved within 10 min during propofol anesthesia. However, more prolonged recovery may occur in the presence of sevoflurane. IMPLICATIONS: We studied the reversal of rapacuronium-induced block with edrophonium and found that the residual rapacuronium block can be readily antagonized during propofol-based anesthesia. However, reversal of rapacuronium appears to be less predictable during sevoflurane-based anesthesia.

Brca1 controls homology-directed DNA repair.

Germline mutations in BRCA1 confer a high risk of breast and ovarian tumors. The role of BRCA1 in tumor suppression is not yet understood, but both transcription and repair functions have been ascribed. Evidence that BRCA1 is involved in DNA repair stems from its association with RAD51, a homolog of the yeast protein involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination. We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination. The relative frequencies of homologous and nonhomologous DNA integration and DSB repair were also altered. The results demonstrate a caretaker role for BRCA1 in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.

Combination of intrathecal sufentanil 10 mug plus bupivacaine 2.5 mg for labor analgesia: is half the dose enough?

UNLABELLED: This controlled, double-blinded, prospective trial of 42 parturients in early labor was conducted to determine whether halving the total amount of intrathecal (i.t.) sufentanil and bupivacaine reduced the incidence of systemic hypotension while providing adequate analgesia with minimal lower limb motor block. Combined spinal-epidural analgesia (CSE) was instituted; Group A (n = 21) received a total of 10 microg of sulfentanil plus 2.5 mg of bupivacaine, whereas Group B (n = 21) received half that dose. Compared with Group B, Group A had a higher incidence of hypotension (nine parturients in Group A, two in Group B; P < 0.05), a greater degree of motor block (P < 0.05), and a higher incidence of sedation (nine parturients in Group A were sedated, one in Group B; P < 0.01). Group B had higher pain scores for the first 5 min (P < 0.05) and a lower level of sensory blockade (median of T7 in Group B compared with T4 in Group A; P < 0.01). We conclude that halving the total amount of i.t. 10 microg of sufentanil plus 2.5 mg of bupivacaine is a suitable option for CSE in labor because it reduces the incidence of some side effects, such as hypotension and maternal sedation, without compromising overall high maternal satisfaction. IMPLICATIONS: We showed that adequate labor pain relief could be provided by halving the recommended dose of 10 microg of intrathecal sufentanil plus 2.5 mg of bupivacaine. The larger dose, however, produced faster pain relief, which lasted longer than the reduced dose. The mother and baby were not adversely affected with either dose.