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Background Approximately 30,000 people per annum undergo major, emergency abdominal, gastrointestinal surgery, of which 36% (~10,800) are carried out for emergency colorectal pathology. Approximately 14% of all patients requiring emergency surgery undergo laparoscopic surgery. Aims The aims of the LaCeS feasibility trial (Laparoscopic versus Open Colorectal Surgery in the Acute Setting) were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III randomised controlled trial with a comparison of emergency laparoscopic with open surgery for acute colorectal pathology. Methods LaCeS was designed as a prospective, multicentre, single blind, parallel group, pragmatic, randomised controlled feasibility trial with an integrated qualitative study. Randomisation was performed centrally with patients being randomised on a 1:1 basis between laparoscopic or open surgery. Results A total of 64 patients were recruited across 5 centres. The overall average steady state recruitment rate was 1.2 patients/month. Baseline compliance for clinical and HrQoL data was 99.8% and 93.8% respectively. The conversion rate from laparoscopic to open surgery was 39.4% (95% CI 22.9% – 57.9%). The 30 day post-operative complication rate was 27.3% (95% CI 13.3- 45.5) in the laparoscopic arm and 41.9% (95% CI 24.6 – 60.9) in the open arm. Discussion The LaCeS feasibility trial has demonstrated that it is possible to evaluate laparoscopic surgery in the emergency colorectal setting within the context of a randomised controlled trial. LaCeS has demonstrated that it is possible to recruit to a surgical trial in the emergency setting, with good compliance to trial procedures and processes, and overall acceptability by patients and clinicians. The safety data obtained for laparoscopic emergency colorectal surgery indicate an acceptable safety profile, particularly when considering it to that observed in the open arm. Trial Registration ISRCTN15681041 https://doi.org/10.1186/ISRCTN15681041. Funding body: National Institute of Health Research – Research for Patient Benefit

There are few data on whether immunomodulator therapy attenuates humoral response to vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some vaccines require two doses for maximum protection, with international variation in dosing schedules. A 3 month interval between doses is being used in the U.K. We evaluated antibody titres to SARS-CoV-2 following initial-dose BNT162b2 (Pfizer/BioNTech) or AZD1222 (AstraZeneca) vaccines in adults with psoriasis and other immune-mediated inflammatory diseases (IMIDs) receiving biologic and/or oral non-biologic immunomodulators.

Background Treatment of preoperative anaemia is recommended as part of patient blood management, aiming to minimize perioperative allogeneic red blood cell transfusion. No clear evidence exists outlining which treatment modality should be used in patients with colorectal cancer. The study aimed to compare the efficacy of preoperative intravenous and oral iron in reducing blood transfusion use in anaemic patients undergoing elective colorectal cancer surgery. Methods Anaemic patients with non-metastatic colorectal adenocarcinoma were recruited at least 2 weeks before surgery and randomized to receive oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. Perioperative changes in haemoglobin, ferritin, transferrin saturation and blood transfusion use were recorded until postoperative outpatient review. Results Some 116 patients were included in the study. There was no difference in blood transfusion use from recruitment to trial completion in terms of either volume of blood administered (P = 0·841) or number of patients transfused (P = 0·470). Despite this, increases in haemoglobin after treatment were higher with intravenous iron (median 1·55 (i.q.r. 0·93–2·58) versus 0·50 (−0·13 to 1·33) g/dl; P < 0·001), which was associated with fewer anaemic patients at the time of surgery (75 versus 90 per cent; P = 0·048). Haemoglobin levels were thus higher at surgery after treatment with intravenous than with oral iron (mean 11·9 (95 per cent c.i. 11·5 to 12·3) versus 11·0 (10·6 to 11·4) g/dl respectively; P = 0·002), as were ferritin (P < 0·001) and transferrin saturation (P < 0·001) levels. Conclusion Intravenous iron did not reduce the blood transfusion requirement but was more effective than oral iron at treating preoperative anaemia and iron deficiency in patients undergoing colorectal cancer surgery.

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.

Background: Breast cancer is the most common malignancy in women. Surgery remains the most effective treatment. Several perioperative factors, including the surgical stress response, many anesthetics and opioids, adversely affect immune function. Regional anesthesia-analgesia attenuates perioperative immunosuppression. We tested the hypothesis that patients who receive combined propofol/paravertebral anesthesia-analgesia (propofol/paravertebral) exhibited reduced levels of protumorigenic cytokines and matrix metalloproteinases (MMPs) and elevated levels of antitumorigenic cytokines compared with patients receiving sevoflurane anesthesia with opioid analgesia (sevoflurane/opioid). Methods: Primary breast cancer surgery patients were randomized to propofol/paravertebral (n = 15) or sevoflurane/opioid (n = 17) and preoperative and postoperative serum concentrations of 11 cytokines (interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon γ, and tumor necrosis factor α) and 3 MMPs (MMP-1, MMP-3, and MMP-9) were measured. Results: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathologic diagnosis. Pain scores were lower at 1 and 2 hrs with paravertebral analgesia compared with morphine but similar at 24 hrs. Patients in the propofol/paravertebral group showed a greater percentage decrease in postoperative compared with preoperative IL-1β (median [quartiles], −26% [−15% to −52%] versus −4% [−14% to 2%], P = 0.003), a significant attenuation in elevated MMP-3 (2% [−39% to 12%] versus 29% [23%-59%], P = 0.011) and MMP-9 (26% [13%-54%] versus 74% [50%-108%], P = 0.02), and a significant increase in IL-10 (10% [5%-33%] versus −15% [20% to −2%], P = 0.001) compared with sevoflurane/opioid group. No significantly different changes in IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, interferon γ, tumor necrosis factor α, or MMP-1 were observed between the 2 groups. Conclusions: Propofol/paravertebral anesthesia-analgesia for breast cancer surgery alters a minority of cytokines influential in regulating perioperative cancer immunity. Further evaluation is required to determine the significance of these observations.

Background Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. Methods In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. Results After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Conclusions Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

Background and Objectives: There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery. Methods: Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 μg (group LF, 13 patients), or clonidine 150 μg (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentanyl 4 μg/mL (LF), or levobupivacaine 0.05% with clonidine 3 μg/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection. Results: There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) μg/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) μg/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively. Conclusions: After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.

The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra- and postoperative paravertebral analgesia. Patients were randomly allocated to four groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus levobupivacaine 0.25% plus fentanyl 50 microg followed by an infusion of levobupivacaine 0.05% with fentanyl 4 microg x ml(-1); Group LC received 19 ml bolus levobupivacaine 0.25% plus clonidine 150 microg followed by an infusion of levobupivacaine 0.05% with clonidine 3 microg x ml(-1); Group C (control) received general anaesthesia without paravertebral analgesia. All groups received postoperative i.v. morphine patient controlled analgesia (PCA). Although mean (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg] and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p < 0.01, paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension, respectively.

Postoperative nausea and vomiting is common after cardiac surgery and may contribute to significant morbidity. Gastric decompression during anesthesia has been used for postoperative nausea and vomiting prophylaxis in shorter duration noncardiac surgery with conflicting results. We tested the hypothesis that gastric decompression during elective coronary revascularization surgery with cardiopulmonary bypass and continued afterwards until tracheal extubation would reduce the incidence of vomiting or retching and nausea. In a prospective, randomized, cohort study, 104 patients with at least 2 Apfel's risk factors for postoperative nausea and vomiting were allocated to receive a gastric tube on free gravity drainage after induction of anesthesia (n = 52) or to a control group (n = 52). The gastric tube was removed simultaneously with tracheal extubation postoperatively. The primary outcome measure was the incidence of vomiting or retching. Secondary outcomes included the incidence and severity of nausea measured on a visual analog scale. The incidence of vomiting or retching was 13.4% in patients with gastric decompression, compared with 11.5% in the control group (P = 0.7). Similarly, there was no statistically significant difference between the two groups in the incidence of nausea (32.7% versus 25.0%, P = 0.6), median severity of nausea on a visual analog scale at 12 h (25; range, 0-55 mm versus 30; range, 0-60 mm, P = 0.4), or antiemetics administration (38.5% versus 28.8%, P = 0.3). Continuous gastric decompression during coronary revascularization surgery and afterwards until tracheal extubation did not reduce the incidence of vomiting or retching or the incidence and severity of nausea in these patients.

Postoperative cognitive dysfunction (POCD) is evident in 26% of elderly patients seven days after major non-cardiac surgery. Despite the growing popularity of day surgery, the influence of anesthetic techniques on next day POCD has not been investigated. Therefore, we evaluated the incidence of POCD and changes in serum markers of neuronal damage (S-100ss protein and Neuron-Specific Enolase), 24 hr after single-agent propofol or sevoflurane anesthesia in elderly patients undergoing minor surgery.Patients (n = 30, mean age 73, range 65-86 yr) coming for cystoscopy or hysteroscopy, were randomized, in an observer-blind design, to receive either single-agent propofol or sevoflurane anesthesia. Changes in neuropsychological tests (the Stroop test and the modified Word-Recall Test), 24 hr postoperatively were compared with age-matched control subjects (n = 15) using Z-score analysis. Changes in S-100beta protein and Neuron-Specific Enolase levels were also documented.POCD was present in 7/15 [47% (95% confidence interval (CI) 21 to 72%)] patients who received propofol and 7/15 [47% (95% CI 21 to 72%)] patients who received sevoflurane, compared with 1/15 [7% (95% CI 6 to 19%)] control patients, P = 0.03. S-100beta protein and Neuron-Specific Enolase levels were not significantly different in anesthetized patients postoperatively compared with preoperative values.The incidence of POCD in elderly patients on the first day after minor surgery is higher than previously reported for seven days after major surgery, and is increased after both propofol and sevoflurane anesthesia, compared with age-matched controls. S-100beta protein and Neuron-Specific Enolase levels were unaffected by anesthetic technique.

Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (SD) percentage change in VEGF at 4 and 24 h respectively were 3% +/- 44% versus 9% +/- 80%, P=0.29 and 5% +/- 43% versus -10% +/- 63%, P=0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% +/- 17% versus 11% +/- 69%, P=0.29 and 34% +/- 19% versus 47% +/- 18%, P=0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.

A study of Conger conger diet was carried out with 213 specimens from Irish inshore waters (0–200 m) collected from winter 1998 to spring 1999 and 96 from offshore waters (200–600 m) from spring to summer 2000. The primary diet in both areas was fish, with a complete species shift in diet between areas. The dominant species inshore were Merlangius merlangus and offshore Micromesistius poutassou. Decapod crustaceans and cephalopods were observed in stomachs, but contributed little to the overall diet.

Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.

A sample of 166 conger eel, Conger conger (Linnaeus, 1758) were captured between August 1998 and June 1999, from the inshore south coastal waters of Ireland using demersal trawl, longlines, lobster and shrimp pots. The range in length was 33–159 cm and weight was 0.05–12.0 kg. Age, determined from vertebrae and sagittal otoliths, ranged from 4 to 20 years. Vertebrae were found to be the most effective tool for ageing. A linear relationship was found between total length and otolith radius. A curvilinear model best described the relationship between total length and vertebral radius. Both otoliths and vertebrae were used in the back-calculation technique and the von Bertalanffy growth function was fitted. Population growth curves were constructed from both vertebral and otolith measurements. Growth parameters, L∞ and k were estimated for individual fish showing large ranges in values. L∞ from otoliths ranged from 170 to 320 m, and k from 0.01 to 0.09. From vertebrae, L∞ ranged from 130 to 390 m and k from 0.01 to 0.13. Population estimates from otoliths gave results of L∞=271 cm, k=0.037, t0=−1.396 and from vertebrae gave results of L∞=214 cm, k=0.059, t0=−1.960. Condition factor ranged from 0.03 to 1.73 and gonadosomatic index from 0.53 to 7.05. The greatest increase in condition occurred between summer and autumn, while the greatest increase in gonadosomatic index occurred between autumn and winter. It was not possible to determine the sex of the eels from gross gonad appearance. Histological analysis of the gonads revealed that all conger eels were female. The absence of males and of ripe or spent females in the inshore south coastal inshore waters suggests that conger eels leave this region to spawn. This study has provided the first published data on age, growth and gonad development of a population of the species in the Northeast Atlantic.

A data set on intestinal helminth parasites was collected in the course of an 18 year investigation into the biology of eels in Meelick Bay, Lough Derg, River Shannon. This was used to test two hypotheses relating to the composition and structure of intestinal helminth communities, namely that eels in large rivers do not harbour richer and more diverse communities than those in small rivers but that community composition and structure are more stable over time than in small rivers. The helminth community was species poor, with only six species comprising the component community and a maximum infracommunity richness of three species. The community was overwhelmingly dominated by the acanthocephalan Acanthocephalus lucii, reflecting the importance of its intermediate host Asellus aquaticus in the eels' diet. The remaining helminth species contributed to species richness but made very little contribution to community diversity. Population levels of Acanthocephalus lucii fell and remained low between 1992 and 2000, probably reflecting increased movement of eels from other parts of the lough into Meelick Bay. Diversity values were low, but similar to those reported from other rivers in Britain and Europe. The results provided support for both hypotheses and indicated that in respect of richness, diversity and dominance, the helminth communities of eels in the River Shannon were typical of, and comparable to, those of other large rivers throughout Europe.

Sever, D. M., Halliday, T. R., Moriarty, E. C. and Arano, B. 2000. Sperm storage in females of the smooth newt ( Triturus v. vulgaris L.): II. Ultrastructure of the spermathecae after the breeding season. — Acta Zoologica (Stockholm) 82 : 49‐56. Sperm storage in cloacal spermathecae was studied in females of Triturus v. vulgaris from southern England killed at the end of the breeding season in June. This species mates and oviposits eggs in ponds from March to June. Included in the sample were 12 unmated females collected in terrestrial situations in March and mated in the laboratory. Some of these females oviposited viable eggs in the laboratory whereas others did not oviposit after mating. In addition, we examined five females with unknown mating histories that were collected from a breeding pond in June. We found that all of the specimens contained some stored sperm and were similar in spermathecal ultrastructure. The spermathecae exhibited characteristics of secretory epithelium at the end of a cycle, including irregular heterochromatic nuclei surrounded by scant cytoplasm, absence of organelles involved in synthetic activities, few secretory vacuoles, and wide intercellular canaliculi. Spermiophagy by the spermathecal epithelium was extensive. In contrast, spermathecae from females at the beginning of the breeding season as reported in our previous study were actively producing a PAS+ secretion and did not exhibit spermiophagy. Spermi ophagy is a means of eliminating sperm prior to the next breeding season.

The caves near Naracoorte, South Australia, contain one of the richest and most diverse fossil faunal assemblages on the Australian continent. Three sites were selected for electron spin resonance (ESR) dating because clastic, fossiliferous sediments were sandwiched between speleothem layers. This allows independent age control by highly precise thermal ionization mass-spectrometry (TIMS) U-series dating. We find that all ESR results agree within the constraints given by the U-series dates, and allow further refinement of the age of the fauna analysed, indicating that most of the fauna in the large Victoria Cave Fossil Chamber is twice as old as reported previously. Our dating results, spanning from 280 to 500 ka for the Fossil Chamber, Victoria Cave, to about 125 ka for the Grant Hall, Victoria Cave, and 170 to 280 ka for the Fossil Chamber, Cathedral Cave, indicate little change, if any, in the megafaunal assemblage from the early Middle to the early Late Pleistocene. This changed dramatically after the last interglacial, when a large proportion of the megafauna suddenly disappeared. Copyright © 2001 John Wiley & Sons, Ltd.

The limestone caves of the Naracoorte region in South Australia contain extensive deposits of megafauna-rich sediments and intercalated cave formation (speleothems). High-precision thermal ionisation mass spectrometry (TIMS) U/Th dating of flowstones directly associated with several large deposits reveals a distinct cyclicity in the timing of sediment and flowstone depositional events in the Naracoorte caves. This pattern parallels a cyclical alternation of ‘Wet Phases’, and intervening periods with a water deficit over the last 500 ka (Ayliffe et al., 1998. Geology 26, 147). Dates from flowstone interlayers in the fossil deposits coincide with the massive speleothem growth events which characterise Wet Phases. Hiatuses in flowstone deposition correlatable through several cave systems imply that water deficits were initiated by regional aridity during full glacial and then extended into the succeeding warmer, wetter interglacials. Clastic deposits in caverns with restricted entrance shafts correlate with hiatuses, suggesting many of these deposits contain fauna representative of full glacial and interglacial climates. Caverns with small openings have often been sealed from the surface and dating has constrained the length of accumulation episodes in several fossil deposits, one to less than 20 ka. The hydrological regimes and environmental conditions inferred from the timing of speleothem deposition have been used to develop a model for cyclic sediment and bone accumulation in the caverns at Naracoorte over the last 400 ka. The giant Victoria Fossil Chamber deposit accumulated prior to 200 ka and because its entrance is large it may contain faunas representative of all climatic phases. There has been no apparent change in faunal diversity at Naracoorte over at least three glacial–interglacial cycles of the Middle Pleistocene.

A speleothem from Victoria Fossil Cave, South Australia, provides a continuous stable isotope record from 185 to 157 ka. Oxygen isotope analysis indicates that, at commencement of deposition, mean annual temperatures were much lower than at present and that between 178 and 162 ka regional surface temperatures were similar to today. Such high temperatures during an interstadial are surprising but may be attributable to increased continentality due to low sealevels. Carbon isotope analysis indicates the presence of an active vegetation cover dominated by C3 plants during the interstadial while a sparse vegetation dominated by C4 grasses appears to have been dominant during full-glacial conditions. Variations in moisture availability and vegetation productivity are probably closely related to stages in the precessional cycle.

In this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post-induction. Patients receiving diclofenac had significantly lower pruritus scores at 30 min (p = 0.0076), 2, 4, 8 and 24 h postoperatively, as well as significantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the first 24 h was also significantly lower in this group. In conclusion, rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus. It also significantly reduces pain and further analgesic requirements postoperatively.

UNLABELLED Halothane affects synaptic transmission in the rat hippocampus with a 50% effective dose (ED50) correlating with clinical figures for minimum alveolar anesthetic concentration (MAC). Halothane dose-dependently suppresses glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs) in the rat hippocampus. It also inhibits voltage-gated Na+ channels. The anticonvulsant lamotrigine acts as a Na+ channel antagonist and inhibits glutamate release after Na+ channel activation. Given their known similar sites of action, the combination of halothane and lamotrigine may alter the inhibition produced by either drug alone. Extracellular recordings of field EPSPs were obtained from the dentate gyrus in the presence of 100 microM picrotoxin (to block GABAA receptors). Stimulation at 30 Hz (200 ms, pulse duration 0.1 ms, six pulses) allowed us to investigate use-dependent block (UDB). Once a stable equilibrium was established, halothane and lamotrigine were administered via the perfusate, and recordings were collected. Both halothane (n = 12) and lamotrigine (n = 6) exhibited reversible inhibition of the EPSP (ED50 0.28 mM [1.2%] and 100 microM, respectively) at low-frequency stimulation. Slices (n = 6) exposed to halothane 0.2 mM (0.75%), then to lamotrigine, showed reduced sensitivity compared with lamotrigine alone. Halothane 0.2 mM potentiated the control UDB (Pulse 6:31% +/- 11% control versus 20.5% +/- 2.5% halothane 0.75%; P < 0.05; n = 6). Lamotrigine had no effect on control UDB. The combination (n = 6) did not alter UDB effects compared with controls or lamotrigine alone. Halothane may reduce the effect of lamotrigine on glutamate release, either at the receptor or via effects at the inactivated Na+ channel. The site of interaction requires further examination. IMPLICATIONS The general and local anesthetic drugs halothane and lamotrigine act at both the glutamate receptor and the Na+ channels and, in our experiments, independently inhibited synaptic transmission at low-frequency stimulation. Although halothane potentiated control use-dependent block, lamotrigine had no effect. Halothane attenuated the inhibitory dose-dependent effects of lamotrigine on synaptic transmission at a low frequency. The clinical importance of this interaction in patients presenting for anesthesia remains unanswered.

Sperm storage in cloacal spermathecae was studied in females of Triturus v. vulgaris collected early in the breeding season in southern England. Females collected in terrestrial situations, presumably unmated, were mated in the laboratory, and the ultrastructure of the transferred sperm and the spermathecae was observed at various intervals after mating. Sperm from a spermatophore cap lodged in a female's cloacal orifice can migrate into spermathecae within 1 hr after mating. Spherical structures on the axial fibers of some sperm in the cap could indicate immaturity. Disorderly clusters of sperm from the cap are still present in the cloacal chamber 12 hr after mating but are absent 24 hr after mating. During storage, sperm often are in tangled masses in the spermathecal tubules. The sperm are coated with spermathecal secretions, and some sperm nuclei were observed embedded in the spermathecal epithelium. Little evidence for spermiophagy early in the breeding season was found. During oviposition, mazes of sperm occur external to the spermathecal orifices, and sperm may be released in this condition onto eggs as they pass through the cloaca. The tangled clusters in which sperm are found from pick-up to oviposition are hypothesized as an adaptation to reduce the effectiveness of sperm competition from the ejaculates of rival males. Additional studies, using the same protocol and covering the entire cycle of sperm storage, are necessary to enable interspecific comparisons leading to phylogenetic hypotheses. J. Exp. Zool. 283:51–70, 1999. © 1999 Wiley-Liss, Inc.

Background Propofol is a short-acting intravenous anesthetic agent. However, cognitive function remains depressed for several hours thereafter. We have evaluated the ability of nefiracetam, a novel cognition-enhancing agent, to alleviate propofol-induced amnesia in a rodent model of learning. Methods Rats were trained in a one-trial, step-through, light-dark passive avoidance paradigm. Propofol (10 and 75 mg/kg) was administered by the intraperitoneal route at 15 min before training and separately at increasing times in the immediate 0-6 h post-training period (100 and 150 mg/kg). Nefiracetam, 9 mg/kg, was administered by the intraperitoneal route 1 h before training. Animals were tested for recall at the 12 h post-training time, and after their killing, immunocytochemistry was used to determine the increase in hippocampal neuronal polysialylation, an event associated with memory consolidation. Induction and duration of anesthesia induced by propofol was determined using tail pinch and pedal withdrawal reflexes. Results Propofol-induced anterograde amnesia occurred in a dose-dependent manner. Induction of retrograde amnesia required a higher dose of propofol, which anesthetized the animals and was effective only in the immediate 3-h post-training period. In the absence of any evident effect on the onset or duration of anesthesia, nefiracetam prevented both forms of propofol-induced amnesia and preserved the learning-associated changes of neuronal polysialylation state. Conclusions The ability of nefiracetam to prevent propofol-induced anterograde and retrograde amnesia is proposed to be indirect and to result from modulation of gene transcription in a manner that initiates a cascade of events involving protein synthesis leading to synaptic growth associated with the formation of the long-term memory trace.

We describe the stages of non-REM sleep induced by anaesthesia with sevoflurane 8% in oxygen and relate these stages to clinical eye positions. We explored John Snow's observation (1847) that ‘when voluntary movement ceases, with the eyes fixed in an upward gaze during the gas induction of anaesthesia, the patient is protected against the risk of mental suffering’ (awareness). Unpremedicated ASA 1 patients undergoing elective tonsillectomy were studied using EEG polysomnographic principles and clinical eye movement tracking. The results expressed as median and range were: latency to stage 1 sleep 4.5 min [2.5–7.5], stage 2 sleep 5 min [3.5–8.5], stage 3 sleep 5.5 min [4–12] and stage 4 sleep 6 min [4.5–15.5]. Eye position 5, the point of no further eye movement, was reached after 9 min [5.5–18.5]. This was significantly longer than the time taken to reach the stage 4 sleep EEG, p

The cross-sectional area of the common carotid artery bulb was measured using a 5 MHz pulse wave Doppler probe in a patient undergoing general anaesthesia using a laryngeal mask airway (LMA). A simultaneous measurement of blood velocity was performed to allow determination of the blood flow. Following inflation of the cuff on the LMA, the cross-sectional area of the right carotid artery bulb decreased from 1.09 to 0.89 cm 2 , flow velocity increased 120 to 176 cm s −1 and the blood flow increased from 130.8 to 156.6 cm 3 s −1 . On the left the cross-sectional area decreased from 1.16 to 1.13 cm 2 , the velocity increased 136 to 151 cm s −1 and the blood flow increased from 157·8 to 170·6 cm 3 s −1 . While a reduction in cross-sectional area was observed in the carotid bulb in this patient, this was accompanied by an increase in the velocity and a consequent increase in blood flow. In patients with atheromatous disease involving the carotid arteries this decrease in cross-sectional area may prove clinically significant. The use of the LMA may not be suitable for this population.

– A total of 8,903 eels were collected in 503 fyke-net samples during the months March to December from 1981 to 1994 in a small bay in Lough Derg, a mesotrophic lake. Variations in catch between months and between years are described. In addition to expected decreases in catch in the colder months, a regular reduction was observed in June. Low catches were observed from 1985 to 1987, coinciding with low water temperatures. A very low catch in August 1994 may have been a chance variation but could have been a first indication of the effects of poor recruitment or of increased commercial fishing effort. The results support the initial hypothesis that a long-term study is required to determine the extent of variation in an eel population.

The Mallampati classification is a commonly used means of preoperatively predicting a difficult endotracheal intubation.As the laryngeal portion of the laryngeal mask airway (LMA) must sit over the larynx, we wondered whether the Mallampati classification also predicts difficulty in achieving adequate seating of the LMA. LMA positioning was assessed prospectively in 100 adult patients by fiberoptic bronchoscopy to determine whether there was a relationship between the ease of seating of the LMA and the Mallampati classification. In 72 patients, optimal seating of the LMA was achieved on the first attempt at insertion, and all these patients were classified as Mallampati class 1 or 2. In all 28 cases of difficulty with LMA insertion, the patients were Mallampati class 2 or 3. In two cases the LMA was abandoned, and in these cases both patients were Mallampati class 3, (P = 0.0001 by chi squared analysis). We conclude that the Mallampati classification indicates difficulty not only in tracheal intubation but also in achieving an adequate airway with the LMA. (Anesth Analg 1995;81:1001-4)

Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. [p]In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i. e. μ, δ- or k-) is at present unknown. [p]Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.

Background Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia–analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro . Methods Patients were randomized to receive propofol/paravertebral anaesthesia–analgesia (propofol/paravertebral, n =11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n =11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured. Results Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (−24% vs 73%, P =0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups. Conclusions Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro , to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia–analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia.In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen.After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia.Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.