Development and evaluation of a novel pre-operative surgery school and behavioural change intervention for patients undergoing elective major surgery: Fit-4-Surgery School.

Group pre-operative education has usually been limited to conditioning expectations and providing education. Prehabilitation has highlighted modifiable lifestyle factors that are amenable to change and may improve clinical outcomes. We instituted a pre-operative 'Fit-4-Surgery School' for patients scheduled for major surgery, to educate and promote healthy behaviour. We evaluated patients' views having attended the school, and after surgery we asked how it had changed their behaviour with a lifestyle questionnaire. The school was launched in May 2016 and was attended by 586/1017 (58%) of invited patients. Patients who did not attend: lived further away, median (IQR [range]) 8 (4-19 [0-123]) miles vs. 5 (3-14 [0-172]) miles, p < 0.001; and were more deprived, Index of Multiple Deprivation Rank decile median (IQR [range]), 6 (4-8 [1-10]) vs. 7 (4-9 [1-10]), p = 0.04. Of the 492/586 (84%) participants who completed an evaluation questionnaire, 462 (94%) would recommend the school to a friend having surgery and 296 (60%) planned lifestyle changes. After surgery, 232/586 (40%) completed a behavioural change questionnaire, 106 (46%) of whom reported changing at least one lifestyle factor, most commonly by increasing exercise. The pre-operative school was acceptable to patients.

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Bilateral versus unilateral botulinum toxin injections for chronic anal fissure: a randomised trial.

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.

Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease.

Objective The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking.

Molecular and biochemical characterisation and recognition by the immune host of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) of the abomasal nematode parasite Teladorsagia circumcincta.

A 1023 bp full length cDNA encoding Teladorsagia circumcincta GAPDH (TeciGAPDH) was cloned, expressed in Escherichia coli and the recombinant protein purified and its kinetic properties determined. A phylogenetic tree was constructed using helminth GAPDH sequences. The predicted protein consisted of 341 amino acids and was present as a single band of about 38 kDa on SDS-PAGE. Multiple alignments of the protein sequence of TeciGAPDH with homologues from other helminths showed that the greatest similarity (93%) to the GAPDH of Haemonchus contortus and Dictyocaulus viviparus, 82-86% similarity to the other nematode sequences and 68-71% similarity to cestode and trematode enzymes. Substrate binding sites and conserved regions were identified and were completely conserved in other homologues. At 25 °C, the optimum pH for TeciGAPDH activity was pH 8, the Vmax was 1052 ± 23 nmol min-1 mg-1 protein and the apparent Km for the substrate glyceraldehyde-3-phosphate was 0.02 ± 0.01 mM (both mean ± SD, n = 2). Antibodies in both serum and saliva from field-immune, but not nematode-naïve, sheep recognised recombinant TeciGAPDH in enzyme-linked immunosorbent assays. The recognition of the recombinant protein by antibodies generated by exposure of sheep to native GAPDH indicates similar antigenicity of the two proteins.

Molecular and biochemical characterisation and recognition by the immune host of the enolase of the abomasal nematode parasite Teladorsagia circumcincta.

A 1299 bp full length cDNA encoding Teladorsagia circumcincta enolase (TeciENO) was cloned, expressed in Escherichia coli and the recombinant protein purified and its kinetic properties determined. Helminth enolase sequences were used to construct a phylogenetic tree. The predicted protein consisted of 433 amino acids and was present as a single band of about 50 kDa on SDS-PAGE. Multiple alignments of the protein sequence of TeciENO with homologues from other helminths showed 98% similarity with Haemonchus contortus enolase, 78-95% similarity to other nematode sequences and 72-75% similarity to cestode and trematode enolases. Substrate binding sites and conserved regions were identified and were completely conserved in other homologues. The optimum pH for TeciENO activity at 25 °C was pH 7, the Km for 2-phophoglycerate 0.09 ± 0.04 mM and the Vmax was 604 ± 6 nmol min-1 mg-1 protein (both mean ± SD, n = 2). TeciENO activity was inhibited by 11.5% by 1 mM citrate (p < 0.001). Antibodies in both serum and saliva from field-immune, but not nematode-naïve, sheep recognised recombinant TeciENO in enzyme-linked immunosorbent assays. The recognition of the recombinant protein by antibodies generated by exposure of sheep to native enolase indicates similar antigenicity of the two proteins.

Excretory/secretory products of adult Haemonchus contortus and Teladorsagia circumcincta which increase the permeability of Caco-2 cell monolayers are neutralised by antibodies from immune hosts.

The onset of abomasal pathophysiology due to parasitism coincides with the presence of adult worms in the lumen, implicating worm excretory/secretory (ES) products acting on the surface mucosa. Caco-2 cell monolayers were grown to confluence on Transwell plates and exposed on the apical side to ES products of adult Haemonchus contortus and Teladorsagia circumcincta. ES products of both species significantly (p<0.001) reduced transepithelial electrical resistance after 2h to 81.1±1.0% and 82.9±1.1% respectively. Immunocytochemical staining of the Caco-2 monolayers for zona occludens-1 and occludin confirmed that the tight junctions remained intact in control medium, but these proteins were internalised from disrupted junctions after exposure to ES products. The components of H. contortus ES products responsible for increased epithelial permeability were partially blocked by phage displaying single chain antibodies derived from sheep immune to field infection and enriched by panning with H. contortus ES products. Immune hosts may therefore be able to reduce the effects of worm chemicals on the gastric epithelium. Permeabilisation of the abomasal surface mucosa by worm chemicals would also explain how cells deep in the gastric glands could rapidly be affected by parasites emerging from the glands or within a day of transplantation of adult worms into naïve hosts, resulting in the pathophysiology typically caused by abomasal nematode parasitism.

Use of fluorescent lectin binding to distinguish eggs of gastrointestinal nematode parasites of sheep.

The binding of a panel of 19 lectins to carbohydrates on the eggs of economically important nematode parasites of sheep has been assessed as the basis of a rapid test to distinguish parasite eggs, at least at the genus level. A total of six lectins can be used to identify eggs of six nematode parasites: peanut agglutinin (PNA) for Haemonchus contortus; Lens culinaris agglutinin (LCA) for Teladorsagia sp; Aleuria aurantia agglutinin (AAL) for Trichostrongylus sp; Psophocarpus tetragonolobus­II (PTLII) for Nematodirus sp; Lotus tetragonolobus lectin (LTL) for Cooperia sp and wheat germ agglutinin (WGA) for Chabertia ovina. For WGA, LCA and LTL, weak binding was also observed to H. contortus and Teladorsagia sp, Trichostrongylus sp and C. ovina eggs, respectively. Nematode eggs in two faecal samples were identically identified by both lectin binding and PCR, except for PCR identification of the eggs of Nematodirus sp, as these did not lyse. Lectins bound best to H. contortus eggs extracted from fresh faecal samples or after storage at room temperature or 4 °C for up to 24 h, but eggs stored at -20 °C or -80 °C did not bind PNA.

Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte-derived dendritic cells.

The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy.

Molecular and biochemical characterisation of abomasal nematode parasites Teladorsagia circumcincta and Haemonchus contortus phosphofructokinases and their recognition by the immune host.

Full length cDNAs encoding phosphofructokinase (PFK) were cloned from Teladorsagia circumcincta (TcPFK) and Haemonchus contortus (HcPFK). TcPFK (2361 bp) and HcPFK (2367 bp) cDNA encoded 787 and 789 amino acid proteins respectively. The predicted amino acid sequences showed 98% similarity with each other and 70% with a Caenorhabditis elegans PFK. Substrate binding sites were completely conserved in both proteins. Soluble N-terminal His-tagged PFK proteins were expressed in Escherichia coli strain BL21, purified and characterised. The recombinant TcPFK and HcPFK had very similar kinetic properties: the pH optima were pH 7.0, Km for fructose 6-phosphate was 0.50 ± 0.01 and 0.55 ± 0.01 mM respectively when higher (inhibiting concentration, 0.3 mM) ATP concentration was used and the curve was sigmoidal. The Vmax for TcPFK and HcPFK were 1110 ± 16 and 910 ± 10 nM min(-1 )mg(-1) protein respectively. Lower ATP concentration (non-inhibiting, 0.01 mM) did not change the Vmax for TcPFK and HcPFK (890 ± 10 and 860 ± 12 nM min(-1 )mg(-1) protein) but the substrate affinity doubled and Km for fructose 6-phosphate were 0.20 ± 0.05 and 0.25 ± 0.01 mM respectively. Recognition of TcPFK and HcPFK by mucosal and serum antibodies in nematode exposed animals demonstrates antigenicity and suggests involvement in the host response to nematode infection.

A multiplex PCR-based method to identify strongylid parasite larvae recovered from ovine faecal cultures and/or pasture samples.

A multiplex PCR-based method was developed to overcome the limitations of microscopic examination as a means of identifying individual infective larvae from the wide range of strongylid parasite species commonly encountered in sheep in mixed sheep-cattle grazing situations in New Zealand. The strategy employed targets unique species-specific sequence markers in the second internal transcribed spacer (ITS-2) region of ribosomal DNA of the nematodes and utilises individual larval lysates as reaction templates. The basic assay involves two sets of reactions designed to target the ten strongylid species most often encountered in ovine faecal cultures under New Zealand conditions (viz. Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus spathiger, Chabertia ovina, and Oesophagostomum venulosum). Five species-specific primers, together with a pair of "generic" (conserved) primers, are used in each of the reactions. Two products are generally amplified, one by the generic primer pair regardless of species (providing a positive PCR control) and the other (whose size is indicative of the species present) by the appropriate species-specific primer in combination with one or other of the generic primers. If necessary, any larvae not identified by these reactions can subsequently be tested using primers designed specifically to detect those species less frequently encountered in ovine faecal cultures (viz. Ostertagia ostertagi, Ostertagia leptospicularis, Cooperia punctata, Nematodirus filicollis, and Bunostomum trigonocephalum). Results of assays undertaken on >5500 nematode larvae cultured from lambs on 16 different farms distributed throughout New Zealand indicated that positive identifications were initially obtained for 92.8% of them, while a further 4.4% of reactions gave a generic but no visible specific product and 2.8% gave no discernible PCR products (indicative of insufficient or poor quality DNA template). Of the reactions which yielded only generic products, 91% gave positive identifications in an assay re-run, resulting in a failure rate of just ∼ 0.4% for reactions containing amplifiable template. Although the method was developed primarily to provide a reliable way to identify individual strongylid larvae for downstream molecular applications, it potentially has a variety of other research and practical applications which are not readily achievable at present using other methods.

Molecular and biochemical characterisation of arginine kinases in Haemonchus contortus and Teladorsagia circumcincta.

Full length cDNA encoding arginine kinases (AK) were cloned from Teladorsagia circumcincta (TcAK) and Haemonchus contortus (HcAK). The TcAK and HcAK cDNA (1080 bp) encoded 360 amino acid proteins. The predicted amino acid sequence showed 99% similarity with each other and 94% with a Caenorhabditis elegans AK. Soluble N-terminal His-tagged AK proteins were expressed in Escherichia coli strain BL21, purified and characterised. All binding sites were completely conserved in both proteins. The recombinant TcAK and HcAK had very similar kinetic properties: K(m) arginine was 0.35 mM, K(m) ATP was 0.8-0.9 mM and the pH optima were pH 7.5. Arginine analogues strongly inhibited recombinant enzyme activities (up to 80%), whilst other amino acids decreased activities by a maximum of 20%. TcAK and HcAK are potential vaccine candidates because of the strong antigenicity of invertebrate phosphagens and kinases and presence in metabolically active parts of the worm.

Sarcosine metabolism in Haemonchus contortus and Teladorsagia circumcincta.

Sarcosine (N-methylglycine) is an intermediate in glycine degradation and can also be synthesised from glycine in mammals. Sarcosine metabolism in Haemonchus contortus and Teladorsagia circumcincta differed from that of mammals in that creatinase activity was present and sarcosine was demethylated only by sarcosine oxidase (SOX) and not by sarcosine dehydrogenase (SDH). The mean SOX activity was 30 nmolmin(-1)mg(-1) protein in homogenates of L3 and adult worms of both parasites and the apparent Km for sarcosine was 1.1 mM. Addition of 2 mM Cd(2+) inhibited activity by 30%. There was no SDH activity with either NAD(+) or NADP(+) as co-factor. Mean creatinase activity in L3 T. circumcincta and adult worms of both species was 31±6 nmolmin(-1)mg(-1) protein, but was undetectable in L3 H. contortus. Activity was inhibited by up to 70% by Cu(2+), Fe(2+), Fe(3+) and Zn(2+). Possessing creatinase would allow host creatine to be incorporated into amino acids by the parasites.

Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens.

Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression. The mutational profile in the fetuses is similar to postnatal and immunized calves, with targeting of complementarity-determining region (CDR) over framework region (FR), preference of replacement over silent mutations in CDRs but not in FRs, and targeting of the AID hotspot motif RGYW/WRCY. Statistical analysis indicates negative selection on FRs and positive selection on CDRs. Our results suggest that AID-mediated somatic hypermutation and selection take place in bovine fetuses, implying a role for AID in the diversification of the primary antibody repertoire in the absence of exogenous antigens.

A prospective case-control study of extralevator abdominoperineal excision (ELAPE) of the rectum versus conventional laparoscopic and open abdominoperineal excision: comparative analysis of short-term outcomes and quality of life.

BACKGROUND: Conventional abdominoperineal excision (APE) of the rectum is associated with higher circumferential resection margin (CRM) involvement, increased local recurrence, and reduced survival compared to anterior resection. A more radical extralevator APE (ELAPE) technique may improve oncological outcome. However, this technique may confer additional morbidity, and little comparative data on short-term outcomes have been reported. This study compares short-term outcomes and quality of life (QOL) after open and laparoscopic ELAPE, laparoscopic APE (LAPE), and open APE (OAPE). METHODS: Data on all ELAPE and 10 consecutive LAPE and OAPE were extracted from a prospective database. Perioperative care and follow-up were standardized. QOL was assessed using EORTC questionnaires. RESULTS: Sixteen ELAPE (14 laparoscopic), 10 LAPE, and 10 OAPE were included. Demographics, tumour stage, and neoadjuvant therapy use were comparable. Operative time was higher with ELAPE than LAPE and OAPE (295, 207.5, and 157.5 min, respectively, p = 0.01). A porcine collagen perineal mesh was used in 9 patients undergoing ELAPE but in no LAPE or OAPE patients. No difference in 30-day complications, re-admission, or length of stay was noted. ELAPE and LAPE were associated with earlier removal of urinary catheter (p = 0.02), yet other enhanced recovery after surgery (ERAS) parameters were equivalent. All ELAPE resections were R0 with no positive CRM identified. One LAPE and 2 OAPE were R1 resections. Analysis revealed no deterioration in QOL with ELAPE, with equivalent global health status. CONCLUSIONS: The results of this study suggest that ELAPE is not associated with deterioration in short-term outcomes or QOL when compared with LAPE or OAPE.

A meta-analysis of the effectiveness of the opioid receptor antagonist alvimopan in reducing hospital length of stay and time to GI recovery in patients enrolled in a standardized accelerated recovery program after abdominal surgery.

BACKGROUND: Despite accelerated recovery programs and the widespread uptake of laparoscopic surgery, postoperative ileus remains a significant factor affecting length of stay after abdominal surgery. Alvimopan, an opioid-receptor antagonist, may reduce the incidence of postoperative ileus and expedite hospital discharge. OBJECTIVE: The aim of this study was to perform a meta-analysis to determine the role of alvimopan in accelerating GI recovery and hospital discharge after laparoscopic and open abdominal surgery performed within an accelerated recovery program. DATA SOURCES AND STUDY SELECTION: Cochrane (1999-2010), Embase (1980-2010), MEDLINE (1980-2010), and International Pharmaceutical Abstracts (1970-2010) were searched for relevant double-blinded, randomized controlled trials. INTERVENTIONS: Twelve milligrams of alvimopan and placebo were given to patients enrolled in an accelerated recovery program after abdominal surgery. MAIN OUTCOME MEASURES: The primary outcomes measured were the length of stay as defined by the writing of the hospital discharge order and GI-3 and GI-2 GI tract recovery. RESULTS: : Three trials were included that reported on a pooled modified intention-to-treat population of 1388 patients; 685 (49%) patients received alvimopan. On meta-analysis, alvimopan reduced time to the hospital discharge order (HR 1.37 (1.21, 1.62), p < 0.0001), GI-3 recovery (HR 1.42 (1.25, 1.62), p < 0.001), and GI-2 recovery (HR 1.49 (1.32, 1.68), p < 0.0001). LIMITATIONS: The search criteria identified only a small number of trials of alvimopan after abdominal surgery with no randomized trials of alvimopan after laparoscopic surgery. In addition, the use of length of hospital stay as the primary outcome measure may be inappropriate, because it is open to many confounding factors. Finally, adverse events, in particular, adverse cardiovascular events, were not considered. CONCLUSIONS: Alvimopan 12 mg can further reduce time to GI recovery and hospital discharge in patients undergoing abdominal surgery within an accelerated recovery program. Investigation into the effect of alvimopan following laparoscopic surgery and additional cost-benefit analyses are required to further define the role of this intervention.

Early experience with laparoscopic extralevator abdominoperineal excision within an enhanced recovery setting: analysis of short-term outcomes and quality of life.

INTRODUCTION: Conventional abdominoperineal excision for low rectal cancer has a higher local recurrence and reduced survival compared to anterior resection. An extralevator abdominoperineal excision (ELAPE) may improve outcome through removal of increased tissue in the distal rectum. Experience with ELAPE is limited and no studies have reported on quality of life (QOL) following this procedure. We describe a minimally invasive approach to ELAPE within an enhanced recovery programme, and present short-term results and QOL analyses. METHODS: All laparoscopic ELAPEs were included in a prospective database. Demographics, intra-operative and post-operative outcomes were evaluated. Postoperative QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-CR29. RESULTS: Thirteen laparoscopic ELAPEs were performed over a two-year period. All were enrolled in an enhanced recovery programme. The median age was 76. The median tumour height was 20 mm (range: 0-50 mm) from the dentate line and all patients received neoadjuvant treatment. The median duration of surgery was 300 minutes (range: 120-488 minutes), the mean blood loss was 150 ml and one procedure was converted to open surgery. There was no circumferential resection margin involvement or tumour perforation. The median duration of use of intravenous fluid, patient controlled analgesia and urinary catheterisation was 2, 2 and 2.5 days respectively and the median length of hospital stay was 7.5 days. Two patients developed perineal wound dehiscence. QOL analysis revealed high global health status (90.8), physical (91.3), emotional (98.3) and social functioning (100) scores, which compared favourably with EORTC reference values and published QOL scores following conventional abdominoperineal excision. CONCLUSIONS: Laparoscopic ELAPE within an enhanced recovery setting is a feasible and safe approach with acceptable short-term outcomes and post-operative quality of life.

Molecular and biochemical characterisation of a Teladorsagia circumcincta glutamate dehydrogenase.

A full length cDNA encoding glutamate dehydrogenase was cloned from Teladorsagia circumcincta (TcGDH). The TcGDH cDNA (1614 bp) encoded a 538 amino acid protein. The predicted amino acid sequence showed 96% and 93% similarity with Haemonchus contortus and Caenorhabditis elegans GDH, respectively. A soluble N-terminal 6xHis-tagged GDH protein was expressed in the recombinant Escherichia coli strain BL21 (DE3) pGroESL, purified and characterised. The recombinant TcGDH had similar kinetic properties to those of the enzyme in homogenates of T. circumcincta, including greater activity in the aminating than deaminating reaction. Addition of 1mM ADP and ATP increased activity about 3-fold in the deaminating reaction, but had no effect in the reverse direction. TcGDH was a dual co-factor enzyme that operated both with NAD(+) and NADP(+), GDH activity was greater in the deaminating reaction with NADP(+) as co-factor and more with NADH in the aminating reaction.

National UK audit of procedure for prolapsing haemorrhoids on behalf of the Association of Coloproctology of Great Britain and Ireland.

OBJECTIVE: To assess the safety and short term outcomes of the procedure for prolapsing haemorrhoids (PPH), a relatively new procedure for the treatment of symptomatic haemorrhoids. METHOD: In 2005, the Association of Coloproctology of Great Britain and Ireland set up an online electronic database to audit the indications and outcomes for patients undergoing a PPH procedure. RESULTS: During the audit period, 695 patients were entered onto the database by 61 surgeons (range 1-50 patients per surgeon). The main indications for surgery were bleeding (90.5%) and prolapse (83.9%). Three hundred and ninety-seven (57.1%) patients had grade III or IV haemorrhoids. PPH was performed under general anaesthetic in 602 (86.6%) cases and a consultant surgeon performed the procedure in 572 (82.3%) cases. The median length of stay was 1 day (range 0-6 days). Two hundred and eighty-nine (41.6%) procedures were performed as a day case. Immediate complications were recorded in 75 (10.8%) patients, the commonest being bleeding (21) and urinary retention (24). At 6-week follow-up, 626 (90.1%) patients were pain free. Five patients required hospital re-admission for secondary haemorrhage (3), peri-anal abscess (1) and pain (1). The commonest problems were minor bleeding (48), urgency (22), pain (14), continued prolapse (12) and pruritus (11). Four patients required an open haemorrhoidectomy for persistent symptomatic haemorrhoids. CONCLUSION: Procedure for PPH is a safe and effective procedure for symptomatic haemorrhoids with good short-term outcomes. Long-term follow-up is required perhaps through a compulsory national register.

A double-blind randomised trial to evaluate the effect of anastrozole for the treatment of non-toxic multinodular goitre.

Multinodular goitre (MNG) is a common clinical finding, particularly in females and is usually asymptomatic. When symptoms occur because of local pressure-related effects the only treatment is surgical involving partial or total thyroidectomy. A number of epidemiological observations and experimental data have suggested that oestrogen aromatase activity may be involved in the pathogenesis of MNG. This study examines the effect of anastrozole, a non-steroidal aromatase inhibitor that inhibits the peripheral conversion of testosterone to oestradiol, in reducing the size of MNG. Thirty-two post-menopausal female patients, median age 63 years (range 42-84) were randomised in a double-blind fashion to receive either anastrozole 1 mg daily or placebo for 3 months. Ultrasonographic measurement of each thyroid lobe and isthmus together with complete biochemical and hormone profiles were performed at the start and end of treatment. There was no significant reduction in the goitre size for patients in the anastrozole group (p = 0.246) or the placebo group (p = 0.418). There were no significant changes in hormone profiles (including throglobulin concentration) within each group between the start and end of the study. We conclude that the use of anastrozole in the treatment of MNG does not appear to have any effect in reducing the size of MNG.