Fetal effects of combined spinal-epidural vs epidural labour analgesia: a prospective, randomised double-blind study.

We have compared fetal heart rate patterns, Apgar scores and umbilical cord gas values following initiation of labour analgesia using either combined spinal-epidural or epidural. One hundred and fifteen healthy women requesting neuraxial analgesia in the first stage of labour were randomly assigned to receive either combined spinal-epidural (n = 62) or epidural analgesia (n = 53). Fetal heart rate traces, recorded for 30 min before and 60 min after neuraxial block, were categorised as normal, suspicious or pathological according to national guidelines. Sixty-one fetal heart rate tracings were analysed in the combined spinal-epidural group and 52 in the epidural group. No significant differences were found in fetal heart rate patterns, Apgar scores or umbilical artery and vein acid-base status between groups. However, in both combined spinal-epidural and epidural groups, there was a significant increase in the incidence of abnormal fetal heart rate patterns following neuraxial analgesia (p < 0.0001); two before compared with eight after analgesia in the combined spinal-epidural group and zero before compared with 11 after in the epidural group. These changes comprised increased decelerations (p = 0.0045) (combined spinal-epidural group nine before and 14 after analgesia, epidural group four before and 16 after), increased late decelerations (p < 0.0001) (combined spinal-epidural group zero before and seven after analgesia, epidural group zero before and eight after), and a reduction in acceleration rate (p = 0.034) (combined spinal-epidural group mean (SD) 12.2 (6.7) h(-1) before and 9.9 (6.1) h(-1) after analgesia, epidural group 11.0 (7.3) h(-1) before and 8.4 (5.9) h(-1) after). These fetal heart rate changes did not affect neonatal outcome in this healthy population.

Combined spinal epidural vs epidural labour analgesia: does initial intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?

Labour analgesia initiated using a combined spinal-epidural (CSE) technique may reduce subsequent epidural bupivacaine requirements compared with an epidural-only technique. We compared the minimum local analgesic concentrations (MLAC) of epidural bupivacaine following initial intrathecal or epidural injection. In a prospective, double-blind study, 115 women requesting epidural analgesia were randomly assigned to receive either an epidural with bupivacaine 20 mg and fentanyl 40 µg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 µg. Analgesia was assessed using a visual analogue pain score. When further analgesia was requested, bupivacaine 20 ml was given, and the concentration was determined using the technique of up-down sequential allocation. The MLAC of bupivacaine in the epidural group was 0.032% wt/vol (95% CI 0.020-0.044) compared with 0.047% wt/vol (95% CI 0.042-0.052) in the CSE group. Bupivacaine requirements for the second injection were increased following intrathecal analgesia by a factor of 1.45 (p = 0.026) compared with epidural analgesia.

Arming a replicating adenovirus with osteoprotegerin reduces the tumor burden in a murine model of osteolytic bone metastases of breast cancer.

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anticancer agents designed to infect and lyse tumor cells. However, in spite of their promise as selective cancer therapeutics, replicating adenoviruses have shown limited efficacy in the clinical setting. We hypothesized that a CRAd armed with osteoprotegerin (OPG) would eradicate bone metastases of breast cancer both directly, by oncolysis, and indirectly, by inhibiting osteoclastic bone resorption, and thus reducing the tumor burden. We constructed an armed CRAd (Ad5-Δ24-sOPG-Fc-RGD) by replacing viral E3B genes with a fusion of the ligand-binding domains of OPG and the Fc portion of human IgG1. Conditional replication was conferred by a 24-base pair deletion within E1A (Δ24), which prevents the binding of E1A to the retinoblastoma tumor suppressor/cell cycle regulator protein and limits replication in normal cells. Enhanced infection of cells expressing low levels of the primary Ad5 receptor was conferred by incorporating an arginine-glycine-aspartic acid (RGD) peptide sequence into the fiber knob to mediate binding to α(v) integrins. After characterization of the armed CRAd, we demonstrated that infection of breast cancer cells by Ad5-Δ24-sOPG-Fc-RGD both killed the infected cells by oncolysis and inhibited the formation of osteoclasts in an in vitro co-culture model. In a murine model of osteolytic bone metastases of breast cancer, the CRAd armed with shortened OPG (sOPG)-Fc reduced tumor burden in the bone and inhibited osteoclast formation more effectively than an unarmed CRAd.

A national survey of safe practice with epidural analgesia in obstetric units.

The National Patient Safety Agency (NPSA) identified practice improvements with regard to epidural injections and infusions and released a patient safety alert on 28th March 2007. Prior to this, the Obstetric Anaesthetists' Association had considered the draft document and wished to assess current compliance in UK obstetric units. A postal survey of consultant-led obstetric anaesthetic units in the UK was performed in September 2006 to look at practice prior to the release of the safety alert. The response rate was 89%. Many units are already following the guidance from the NPSA but nearly one in four units have experience of wrong route drug errors related to confusion between systems for intravenous and regional drug administration.

Combined epidural/spinal anaesthesia: needle-through-needle or separate spaces?

BACKGROUND AND OBJECTIVE: This prospective, randomized and blinded study compared the performance of a new needle-through-needle (NTN) kit (Epistar; Medimex, Germany) with the double-space technique for providing combined spinal epidural anaesthesia during Caesarean section. METHODS: Following local Ethics Committee approval and patient consent, 200 females were randomized to receive combined spinal epidural anaesthesia by the double-space (n = 100) or NTN (n = 100) technique. The frequency with which the intrathecal component could achieve a T5 block to touch for Caesarean section without the need for epidural augmentation or an alternative technique was determined. The time from start of procedure to achieving a block height to T5 was recorded. Pain and backache at insertion, and at 24 h follow-up were recorded using a visual analogue scale. To remove any bias due to posture, 50% of each group were further randomized to receive their block in the sitting or in the left lateral position. To evaluate improvement of performance over time the success in the first 100 study patients were compared to the success in the second 100. RESULTS: A successful block to T5 with the double-space and NTN techniques were 80 vs. 54, odds ratio 0.29. Failure to enter the intrathecal space once the epidural space had been located occurred in 29 patients in the NTN group. Time to readiness for surgery was 15 min (95% confidence interval (CI): 12.7-17.4) and 12.9 min (95% CI: 11.5-14.3) for the double-space and NTN techniques, respectively. The median (interquartile range) visual analogue scores for discomfort at insertion were 30 (12.5-51.5) and 32 (12.75-60) and for postoperative backache 0 (0-10) and 0 (0-10.75) in the double-space and NTN groups, respectively. The number of epidural augmentations was similar in both the groups and posture made no difference. There was a tendency to increased success in the second half of the study. CONCLUSION: The double-space technique had a greater success rate than the NTN technique.

Minimum dose of intrathecal diamorphine required to prevent intraoperative supplementation of spinal anaesthesia for Caesarean section.

BACKGROUND: Intraoperative discomfort during spinal anaesthesia for Caesarean section is the commonest cited anaesthetic cause of litigation in obstetric practice. Intrathecal opioids are used to improve intraoperative comfort and postoperative analgesia for these operations. The minimum intrathecal diamorphine dose that prevents intraoperative supplementation requires determination. METHOD: After ethics committee approval, 200 ASA I, II women with > or = 37 weeks gestation and planned for elective Caesarean section under combined spinal-epidural anaesthesia were recruited. They were randomized into four groups to receive hyperbaric bupivacaine 0.5% 12.5 mg with diamorphine 0.2, 0.3, 0.4 or 0.5 mg by intrathecal injection. The need for intraoperative i.v. supplementation with alfentanil, time to first requests for postoperative analgesia, incidence of nausea and vomiting and requirement for antiemetic and antipruritic were noted. RESULTS: Intraoperative supplementation was inversely proportional to the dose of diamorphine used (P=0.004). The ED(95) value for intrathecal diamorphine to prevent intraoperative supplementation was 0.39 mg. Mean time interval for request for postoperative analgesia was 446 min in the 0.2 mg group, 489 min in the 0.3 mg group, 601 min in the 0.4 mg group and 687 min in the 0.5 mg group (P=0.003 for trend). Incidence of nausea, vomiting and pruritus increased with dose of diamorphine used (P values for trend: nausea, 0.04; vomiting, 0.008; pruritus, 0.004). Requests for antiemetic increased with dose but achieved significance only for requirement for second antiemetic (P=0.03). Request for antipruritic did not achieve significance. CONCLUSION: The ED(95) for the amount of intrathecal diamorphine required to prevent intraoperative supplementation during spinal anaesthesia for Caesarean section is 0.4 mg in clinical terms. Times to first requests for analgesia, incidence of nausea, vomiting and pruritus increase with dose.

The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells.

The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

Regional blockade for delivery in women with scoliosis or previous spinal surgery.

We conducted a prospective observational study between 1992 and 2001 identifying obstetric patients with untreated or surgically corrected scoliosis or lumbar-sacral fusion surgery. The regional techniques for labour and delivery that were offered were epidural analgesia, combined spinal epidural anaesthesia (CSE), single shot spinal or continuous spinal anaesthesia (CSA) depending on the degree of scoliosis, previous surgery, cardio-respiratory compromise and planned mode of delivery. Forty women were included in the study, one woman with two separate deliveries, giving 41 cases for analysis. Twenty-four women presented in labour: 11 required no regional technique, seven received effective epidural analgesia and six received CSA. Seventeen women presented for elective caesarean delivery: two received a CSE technique, two received single shot spinal and 13 had CSA. From a total of 19 CSA techniques attempted sixteen catheters were successfully inserted and produced good analgesia or anaesthesia for vaginal or operative delivery in 12 women (63%). There was one case of post dural puncture headache following a CSA for labour and delivery. We discuss the choices available for regional anaesthetic techniques in scoliotic women and the relative merits of each.

High-dose tinzaparin in pregnancy and the need for urgent delivery.

The prolonged anticoagulant effects of high-dose low molecular weight heparin (LMWH) pose problems in pregnant women when unanticipated delivery is required. We present two pregnant women on therapeutic doses of LMWH whose labour did not progress smoothly. The Thrombelastograph coagulation analyser was used to assess the coagulation status periodically. It influenced surgical and anaesthetic management and there was a safe outcome.

Levobupivacaine for epidural analgesia in labor: the sparing effect of epidural fentanyl.

Evidence suggests that levobupivacaine has similar pharmacodynamic properties to racemic bupivacaine. We sought to investigate whether this similarity extends to opioid sparing when levobupivacaine is used for epidural analgesia in laboring women by quantifying the effect of fentanyl on the minimum local analgesic concentration (MLAC) of levobupivacaine. One-hundred-six women requesting epidural analgesia for labor pain were recruited in this randomized, double-blinded, up-down sequential allocation study. Each received 20 mL of one of three test solutions: levobupivacaine control, levobupivacaine and fentanyl 2 microg/mL, or levobupivacaine and fentanyl 3 microg/mL. The initial levobupivacaine concentration was 0.07% wt/vol in each group, with subsequent concentrations of levobupivacaine being determined by the response of the previous patient (testing interval 0.01% wt/vol). Efficacy was accepted if the visual analog score decreased to 10 mm or less on a 100-mm scale within 30 min. The MLAC of levobupivacaine in the control group was 0.091% wt/vol (95% CI, 0.052-0.130). Fentanyl at concentrations of 2 microg/mL and 3 microg/mL significantly reduced the MLAC of levobupivacaine to 0.047% wt/vol (95% CI, 0.023-0.072) and 0.050% wt/vol (95% CI, 0.035-0.065), respectively (P < 0.001). A dose-dependent effect was not demonstrated. We conclude that fentanyl significantly reduces levobupivacaine requirements for epidural analgesia in labor.

Thromboelastography identifies sex-related differences in coagulation.

UNLABELLED: Thromboelastography is an in vitro, point-of-care monitor of whole blood coagulation. Thromboelastography studies have demonstrated a hypercoagulable state during pregnancy. Perhaps the hypercoagulability is attributable to female sex hormones. The aim of the study was to determine if sex, in addition to pregnancy, affected thromboelastography variables by studying male and female (pregnant and nonpregnant) volunteers. Thromboelastography showed significant (P:<0.01) differences in sex, with a significant (P: < 0. 0001) trend of increasing whole blood coagulability from men through nonpregnant to pregnant women. The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men. IMPLICATIONS: The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men.

Training in obstetric general anaesthesia: a vanishing art?

General anaesthesia in obstetric practice has largely been replaced by the use of regional techniques. We have studied this phenomenon and the subsequent impact on training in this technique both retrospectively and with a prospective audit. There has been a decline in the use of general anaesthesia for Caesarean section such that trainee anaesthetists are getting less practical exposure to this important procedure. Audit revealed a deficit with consultant involvement in training and heightened awareness has resulted in improved supervision. Possible implications for future consultant working practices are discussed.

Anaesthesia for caesarean section in a patient with Charcot-Marie-Tooth disease.

We describe the management of a 25-year-old primigravida with severe respiratory insufficiency secondary to CHarcot-Marie-Tooth disease type I scheduled for Caesarean section. Incremental subarachnoid anaesthesia via a microcatheter was utilised. Mother and baby made an uneventful recovery and were discharged home on the tenth postoperative day.

Phenytoin and dyskinesias: a report of two cases and review of the literature.

Dyskinesia is a recognized but uncommon side-effect of treatment with phenytoin. Two additional cases of dyskinesia during treatment with phenytoin are described; both had radiographically documented thalamic infarctions. The reported experience to date with movement disorders induced by phenytoin is reviewed and the clinical features summarized. The available experimental evidence addressing the mechanism underlying this side effect is discussed.

Biologically active metabolites from Xenorhabdus spp., Part 1. Dithiolopyrrolone derivatives with antibiotic activity.

Five related antibiotic compounds, named xenorhabdins, were isolated from cultures of Xenorhabdus spp., bacteria symbiotically associated with insect-pathogenic nematodes. Their chemical structures were elucidated by X-ray crystallography, nmr, and mass spectral analyses to be N-acyl derivatives of either 6-amino-4,5-dihydro-5-oxo-1,2-dithiolo [4,3-b] pyrrole (compounds 1-3) or 6-amino-4,5-dihydro-4-methyl-5-oxo-1,2-dithiolo[4,3-b] pyrrole (compounds 4 and 5). They are previously unreported members of the pyrrothine family of antibiotics. Antimicrobial and insectidical activities were found. These metabolites are specific to phase one Xenorhabdus.

Schistosomiasis in north-western Ghana.

A survey of 8 274 people in the Ghana-2101 project area showed that 12% were passing ova of Schistosoma haematobium in the urine, the infection rate rising to a peak of 34% in males 15-19 years of age. S. mansoni, despite the wide distribution of its potential intermediate host, was not encountered in 1 698 boys examined for it. Urinary schistosomiasis in northern Ghana is focal in character and is usually contracted in standing water during the dry season. A method of control was developed that depends on the identification of localities subject to relatively intense and prolonged transmission, followed by dry season mollusciciding of the water sources in each locality infested with the snail hosts. Two such control cycles were carried out in 30 localities. The results suggest that selective, dry season, focal control of schistosomiasis can be effective in reducing transmission.

The control of guineaworm with abate: a trial in a village of North-West Ghana.

In the village of Gbegru guineaworm infection is contracted by drinking the water of a man-made pond during the dry season. The lethal effect on the vector cyclops of each application of Abate to a concentration of 1 mg/litre lasted 5-7 weeks and was clearly reflected in the following year's incidence of guineaworm cases. This indicates that Abate is potentially useful in the chemical control of guineaworm infection.