Adductor canal versus femoral triangle anatomical locations for continuous catheter analgesia after total knee arthroplasty: a multicentre randomised controlled study.

BACKGROUND: Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption. We hypothesised that AC catheters provide superior functional mobilisation on postoperative Day 1 after TKA as measured using the Timed Up and Go (TUG) test. METHODS: In this multinational, multicentre, double-blinded RCT, catheters were inserted under ultrasound guidance into the anatomical AC and FT compartments. The standardised protocol included spinal anaesthesia without intrathecal morphine, fixed catheter infusion rates, and oral analgesia. RESULTS: Of 151 subjects recruited, 75 were in the AC group and 76 in the FT group. There was no statistically significant difference in TUG on postoperative Day 1 between AC (38 [29-55] s) and FT subjects (44 [32-64] s) (median [inter-quartile range]); P=0.11). There was no difference in TUG Day 2, AC (38 [27-53] s) vs FT (42 [31-59] s); P=0.66. There were no statistically significant differences for secondary endpoints of pain level, effectiveness of pain relief, interference of functional activities and interpersonal relationships by pain, and opioid consumption between groups. CONCLUSIONS: There were no differences in immediate postoperative functional mobility, analgesia, and opioid consumption provided by catheters inserted into the AC vs FT locations for TKA surgery. CLINICAL TRIAL REGISTRATION: ANZCTR12617001421325.

Determination of antimony and barium in UK air quality samples as indicators of non-exhaust traffic emissions.

The aim of this study was to determine concentrations of antimony and barium in air quality samples and assess the potential suitability of these metals as tracer elements for non-exhaust traffic emissions sources. Air quality filters sampled at monitoring sites around the UK for the purposes of the UK Heavy Metals Monitoring Network were subjected to microwave digestion in hydrogen peroxide and nitric acid, then analysed by ICP-MS for a suite of metals including antimony and barium. The average antimony concentration found across all the network sites was 1.84 ng m-3; the average barium concentration was 6.33 ng m-3. The range of antimony concentrations observed was 0.13-8.02 ng m-3; barium concentrations ranged from levels below the detection limit of 0.18 to 39.9 ng m-3. There are no legislative limits for antimony and barium in ambient air, but the maximum concentrations found are well below the Workplace Exposure Limits specified by the UK Health and Safety Executive. The highest concentrations were found at roadside sites situated to monitor traffic environments, supporting the suitability of antimony and barium to be considered tracer elements for traffic emissions sources. Strong correlations were observed between antimony, barium and copper, indicating they share a common traffic-related source. Based on the strong correlation with copper at urban and traffic locations, indicative annual UK atmospheric emission estimates for antimony and barium in brake and tyre wear were calculated as 6 and 19 tonnes respectively.

Novel genomic microsatellite markers for genetic population and diversity studies of tropical scalloped spiny lobster (Panulirus homarus) and their potential application in related Panulirus species.

Fourteen polymorphic microsatellites with perfect di-, tri-, and tetra-nucleotide repeats were identified for Panulirus homarus using Roche 454 whole-genome sequencing method. Microsatellites were efficiently co-amplified in four multiplexes and a singleplex, providing consistent and easily interpretable genotypes. The number of alleles per locus ranged from 2 to 11 with the observed and expected heterozygosity ranging between 0.000-0.532 and 0.031-0.836, respectively. A significant deviation from Hardy-Weinberg equilibrium was observed for majority of the loci, probably due to homozygote excess. Genetic linkage disequilibrium analysis between all the possible pairs of the loci showed significant departure from the null hypothesis in the loci pairs Pho-G11-Pho-G33 and Pho-G33-Pho-G57. High success in primer cross-species amplification of these microsatellite markers indicates their utility for genetic studies of different Panulirus species.

Isolation, characterization, and multiplexing of novel microsatellite markers for the tropical scalloped spiny lobster (Panulirus homarus).

Of the various spiny lobster species in the tropical and subtropical Indo-West Pacific region, the tropical scalloped spiny lobster (Panulirus homarus) supports one of the most commercially valuable fishery resources in many coastal African and Asian countries. The last decade has witnessed a serious decline in the wild populations of this species. Knowledge of the genetic basis of spiny lobster population structure is a prerequisite to achieve a sustainable fisheries management for this species. Here, we describe 13 novel polymorphic microsatellite markers developed for P. homarus, using a cross-species primer design strategy based on P. ornatus Roche 454 shot-gun generated sequencing. Microsatellite polymorphisms were assessed in 96 unrelated P. homarus individuals of a natural population, with the number of alleles per locus varying from 2 to 14, the observed and expected heterozygosity from 0.00 to 0.78 and from 0.03 to 0.79, respectively, and with only four loci (Pho-G27, Pho-G32, Pho-G36, and Pho-G58) deviating from Hardy- Weinberg equilibrium. Genetic linkage disequilibrium analysis between all pairs of the loci showed significant departure from the null hypothesis between loci Pho-G22 - Pho-G30, and Pho-G30 - Pho-G35. The successful cross amplification of these microsatellites highlights the potential of the developed microsatellites for future population genetic research within the different Panulirus species.

The WIMAT colonoscopy suitcase model: a novel porcine polypectomy trainer.

AIM: Simulation allows the acquisition of complex skills within a safe environment. Endoscopic polypectomy has a long learning curve. Our novel polypectomy simulator may be a useful adjunct for training. The aim of this study was to assess its content validity. METHOD: The Welsh Institute for Minimal Access Therapy (WIMAT) endoscopy suitcase was designed to simulate colonic polypectomy. Participants from regional and national courses were recruited into the study. Each undertook a standardized simulated polypectomy and completed a seven-point Likert scale questionnaire examining its realism. RESULTS: In all, 17 participants completed the questionnaire: 15 (88.2%) gastroenterologists, one (5.9%) colorectal surgeon and one (5.9%) experienced endoscopic nurse specialist. Of the gastroenterologists, seven (46.7%) were consultants and eight (53.3%) were senior trainees or Post CCT (Certificate of Completion of Training) fellows. The mean number of real-life polypectomies performed by the cohort was 156 (95% CI 35-355). The highest scores were for 'mucosal realism' (median score 6.0, P=0.001), 'endoscopic snare control' (median score 6.0, P=0.001), 'handling the polyp' (median score 6.0, P=0.001) and 'raising mucosa' (median score 6.0, P<0.001). Of the 15 parameters examined only three were not statistically significant in favour of the simulator. These were 'anatomical realism of sessile polyps', 'resistance of scope movement' and 'paradoxical motion'. The overall score for the simulation was 6.0 (P < 0.001). There was no significant difference between the level of difficulty of the simulator compared with real life (median score 4.0, P = 0.559). CONCLUSION: The WIMAT colonoscopy suitcase model has excellent content validity for several parameters. This may have potential applications in medical training and assessment.

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.

BACKGROUND: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. METHODS: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR. RESULTS: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. CONCLUSION: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC).

BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.

An animal tissue simulation assessing three directional displacement forces on five common tracheostomy securing techniques.

Introduction Several methods of securing a tracheostomy tube have been described in the literature including using ties or tapes around the neck and suturing the plastic flange to the neck in various ways. However, there are no wet lab-based studies to objectively determine the force required to displace the tracheostomy tube using different securing techniques. Ours is the first animal tissue simulation study published in the literature. Methods A simulated tracheostomy stoma was created on a sheep neck model. A tracheostomy tube was inserted into the stoma and secured using various methods. Tension tests were conducted to significantly displace the tube from the stoma. Each technique was repeated six times on different sheep necks. All results were analysed using SPSS®. Results Repeat measurements indicated that the largest displacement forces come from an oblique direction while the lowest force values were found at the lateral angle. Averages of displacement showed that medially placed sutures required the largest forces in comparison with other securing methods. Wilcoxon signed-rank testing indicated that medial and continuous suture security resists displacement at forces that otherwise displace flange and interrupted sutures. Conclusions This study has shown that any type of securing suture requires a greater displacement force than the strap of the tracheostomy tube holder alone. Medially placed sutures require a greater displacement force than those placed laterally. Displacement in the lateral direction requires the least force in comparison with movement at perpendicular or oblique angles.

An audit of imaging test utilization for the management of lymphoma in an oncology hospital: implications for resource planning?

The purpose of this study was to assist with resource planning by examining the pattern of physician utilization of imaging procedures for lymphoma patients in a dedicated oncology hospital. The proportion of imaging tests ordered for routine follow up with no specific clinical indication was quantified, with specific attention to CT scans. A 3-month audit was performed. The reasons for ordering all imaging procedures (X-rays, CT scans, ultrasound, nuclear scan and MRI) were determined through a retrospective chart review. 411 lymphoma patients had 686 assessments (sets of imaging tests) and 981 procedures (individual imaging tests). Most procedures were CT scans (52%) and chest radiographs (30%). The most common reasons for ordering imaging were assessing response (23%), and investigating new symptoms (19%). Routine follow up constituted 21% of the assessments (142/686), and of these, 82% were chest radiographs (116/142), while 24% (34/142) were CT scans. With analysis restricted to CT scans (296 assessments in 248 patients), the most common reason for ordering CT scans were response evaluation (40%), and suspicion of recurrence and/or new symptom (23%). Follow-up CT scans done with no clinical indication comprised 8% (25/296) of all CT assessments. Staging CT scans were under-represented at 6% of all assessments. Imaging with CT scans for follow up of asymptomatic patients is infrequent. However, scans done for staging new lymphoma patients were unexpectedly low in frequency, due to scans done elsewhere prior to referral. This analysis uncovered utilization patterns, helped resource planning and provided data to reduce unnecessary imaging procedures.

Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants.

BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in human liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine receptors CXCR3, CXCR4, and CCR5 on circulating and graft-infiltrating lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. CXCR3 ligands interferon-inducible protein 10 and monokine-induced by gamma interferon were detected on sinusoidal endothelium and interferon-inducible T-cell alpha chemoattractant was detected on portal and hepatic vascular endothelium, whereas the CXCR4 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. CCR5 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional CXCR3, CXCR4, and CCR5 on T cells. Increased expression of chemokine receptors, especially CCR3 and CCR5, was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors CXCR3 and CCR5 are important for recruitment, the restriction of SDF to bile ducts suggests that CXCR4 may be involved in the retention of alloactivated lymphocytes at sites of graft damage.

Audit of decontamination procedures for specialist ophthalmic equipment.

A survey of ophthalmic decontamination protocols in eight district hospitals was undertaken. Procedures differed widely. A literature search revealed only four publications on the subject, all of which dealt with tonometer head disinfection only. After discussion with several manufacturers, whose advice was restricted largely to acrylic lens disinfection and which varied considerably, a local policy for ophthalmic decontamination was established. Nationally agreed disinfection guidelines for high risk ophthalmic instruments are needed.

An evaluation of Cidex OPA (0.55% ortho-phthalaldehyde) as an alternative to 2% glutaraldehyde for high-level disinfection of endoscopes.

Cidex OPA (0.55% ortho-phthalaldehyde) is marketed as a safer alternative to 2% glutaraldehyde for endoscope decontamination. As clinical experience is limited, an evaluation was undertaken in a busy endoscopy unit. Cidex OPA cycle dilution was monitored by manufacturer's test strips and high-pressure liquid chromatography (HPLC). Eight endoscopy staff completed daily occupational health questionnaires before and after its introduction. Patient throughput times were assessed in view of Cidex OPAs reduced disinfection time. HPLC confirmed that Cidex OPA levels are maintained above 0.3% for at least 50 cycles. Indicator strips proved generally reliable when tested by pharmacy staff. However, busy endoscopy staff found the indicator strips difficult to interpret, with 28 out of 223 (12.5%) test results being inappropriately recorded as 'fails'. Two hundred and two questionnaires were completed and no short-term health problems were noted. Apart from bronchoscopy lists, patient turnaround times were not improved. The increased cost of changing to Cidex OPA was estimated as pound 7691 per annum. Staining of washer-disinfectors was of concern as it proved very difficult to remove.

Bacteria-free water for automatic washer-disinfectors: an impossible dream?

The ability of a new automatic washer-disinfector system (AWDS), fitted with a water filtration system to provide bacteria-free water and so avoid the risk of mycobacterial contamination of fibreoptic bronchoscopes, was examined. Four new Astec 'MP' Safescope washer-disinfectors, with coarse and fine (0.2 micron) filters attached close to the outlet taps, were supplied with non-softened mains water. Water samples from the tank supply and outlet taps were regularly assessed for bacterial quality over a six-month period. Outlet samples were also analysed after fine filter change and purgation with peracetic acid. All bronchoalveolar lavage specimens (BALS) were stained and cultured for mycobacteria. Only 13 out of 53 outlet samples (24%) were culture-negative. There was no improvement after filter change. Residual anti-bacterial effect of peracetic acid lasted up to 48 h following AWDS purgation. No tank samples were bacteria-free. Sixty BALS were processed, two samples were culture-positive and grew M. tuberculosis and one was also smear-positive. Though mycobacterial contamination of bronchoscopes was not evident, the water filtration system was unable to reliably provide sterile rinse water.

Psychological change during residence in a rehabilitation centre for female drug misusers. Part II. Children of drug misusers.

This study examined psychological changes in children of female drug misusers who were living with their mothers in a residential rehabilitation centre. The results suggest that the childrens' behaviour and cognitive skills were not adversely affected, and that there were many benefits for drug addicted mothers retaining custody of their children whilst undergoing a rehabilitation programme. The implications of the possible detrimental effects of a mother failing to complete her rehabilitation programme on her children are discussed.

Antifreeze glycoproteins: relationship between molecular weight, thermal hysteresis and the inhibition of leakage from liposomes during thermotropic phase transition.

Antifreeze glycoproteins (AFGP) were isolated and purified from the blood plasma of rock cod (Gadus ogac), using DEAE-Bio-gel ion exchange chromatography, followed by high performance liquid chromatography (HPLC). The purified proteins were analyzed using polyacrylamide gel electrophoresis (PAGE), and electrospray mass spectrometry. The results indicated that rock cod synthesize seven size classes of glycoproteins, ranging from 2.6 to 24 kDa, with each size class containing multiple isoforms. Antifreeze activity, as determined by thermal hysteresis, indicated that the AFGP could be separated into two groups, with the larger size classes (molecular mass>13 kDa) having approximately 3-4 times the activity of the smaller, proline containing, size classes (molecular mass<10 kDa). All of the AFGP size classes prevented leakage from dielaidoylphosphatidylcholine (DEPC) liposomes as they were cooled through their phase transition temperature, with the larger size classes being approximately 4 times as effective as the smaller ones. It is hypothesized that AFGP prevent liposomes from leaking as they pass through the phase transition temperature by binding to the phospholipid membrane.

Inhibition of browning by sulfites.

The present state of understanding of the mechanisms by which sulfites inhibit browning reactions in food is reviewed. The difficulties of specifying the composition of sulfur(IV) oxospecies in sulfited foods arise from the existence of labile equilibria between SO2, HSO3-, SO3(2-) and S2O5(2-), whose position depends on concentration, ionic strength and the presence of non-electrolytes. A proportion of the additive is also found in a reversibly bound form. The main reason why sulfites are able to inhibit a wide range of browning reactions is the nucleophilic reactivity of sulfite ion. The mechanism of reactions between sulfite species and intermediates in the model Maillard browning reaction, glucose + glycine, are considered in depth and are supported by kinetic data. A most interesting feature is the fact that sulfites seem to catalyse the reactions they are added to control. Reaction products include 3,4-dideoxy-4-sulfohexosulose which is formed initially and polymeric substances arise from the reaction of sulfite species with melanoidins. It is found that melanoidins from glucose + glycine react with sulfite to such an extent that one sulfur atom is incorporated for every two glucose molecules used to make up the polymer. The mechanisms of inhibition of ascorbic acid browning, enzymic browning and lipid browning are reviewed briefly. The known toxicological consequences of the formation of reaction products when sulfites are used for the control of Maillard browning give little cause for concern. Little is known of the implications of the formation of reaction products during the inhibition of other forms of browning. Consideration of the requirements for alternatives to sulfites is given.

Proteomic identification of galectin-3 binding ligands and characterization of galectin-3 proteolytic cleavage in human prostasomes.

Galectin-3 is a multifunctional carbohydrate-binding protein that was previously characterized as a proteolytic substrate for prostate-specific antigen (PSA) and was shown to be associated with prostasomes in human semen. Prostasomes are exosome-like vesicles that are secreted by the prostatic epithelium and have multiple proposed functions in normal reproduction and prostate cancer. In the current study, galectin-3 binding ligands in human prostasomes were identified and characterized with the goal to investigate galectin-3 function in prostasomes. Galectin-3 binding proteins were isolated by affinity column chromatography. Candidate ligands identified by MS/MS were PSA, prostatic acid phosphatase (PAP), zinc alpha-2-glycoprotein (ZAG), dipeptidyl peptidase-4 (CD26), aminopeptidase N (CD13), neprilysin, clusterin, antibacterial protein (FALL-39) and alpha-1-acid glycoprotein (ORM1). Biochemical methods were used to characterize the ability of galectin-3 to bind to selected ligands, and galectin-3 cleavage assays were utilized to investigate the protease(s) in prostasomes that cleaves galectin-3. CD26, CD13, PSA, PAP and ZAG immunoreactivity were detected in extracts of purified prostasomes. One-dimensional electroblot analysis of prostasomes demonstrated that CD26, PAP and CD13 immunoreactivity co-migrated with galectin-3-reactive protein bands. PSA and ZAG were found to be associated with the surface of prostasomes. Both intact and cleaved galectin-3 were detected in prostate and prostasome extracts. Cleavage and inhibition assays indicated that PSA in prostasomes proteolytically cleaves galectin-3. The identification of these glycoproteins as galectin-3 ligands lays the groundwork for future studies of galectin-3 and prostasome function in reproduction and prostate cancer.

The new VARSKIN 4 photon skin dosimetry model.

A new photon skin dosimetry model, described here, was developed as the basis for the enhanced VARSKIN 4 thin tissue dosimetry code. The model employs a point-kernel method that accounts for charged particle build-up, photon attenuation and off-axis scatter. Early comparisons of the new model against Monte Carlo particle transport simulations show that VARSKIN 4 is highly accurate for very small sources on the skin surface, although accuracy at shallow depths is compromised for radiation sources that are on clothing or otherwise elevated from the skin surface. Comparison results are provided for a one-dimensional point source, a two-dimensional disc source and three-dimensional sphere, cylinder and slab sources. For very small source dimensions and sources in contact with the skin, comparisons reveal that the model is highly predictive. With larger source dimensions, air gaps or the addition of clothing between the source and skin; however, VARSKIN 4 yields over-predictions of dose by as much as a factor of 2 to 3. These cursory Monte Carlo comparisons confirm that significant accuracy improvements beyond the previous version were achieved for all geometries. Improvements were obtained while retaining the VARSKIN characteristic user convenience and rapid performance.

Retrospective case series analysis of penicillin allergy testing in a UK specialist regional allergy clinic.

INTRODUCTION: Penicillin allergy is the most common drug allergy. Skin testing for the major (PPL) and minor determinants (MDMs) of penicillin offers increased sensitivity and specificity over in vitro testing alone. Following a worldwide absence of reagents, a new kit was licensed in the UK in 2008 (Diater, Spain) and this report evaluates its use in a UK specialist allergy clinic. METHODS: Prospective data on 50 consecutive patients tested with the new reagents were collected. The departmental protocol is adapted from the 2003 EAACI position paper. RESULTS: 14% (7/50) and 12% (6/50) of patients were diagnosed with immediate and non-immediate reactions respectively. The negative predictive value of the PPL and MDM reagents at the neat concentration for an immediate reaction was 93% (true negatives 37, false negatives 3). Two patients experienced systemic reactions to DPT in the absence of demonstrable specific IgE. None of the patients were diagnosed using skin prick testing alone or at lower concentrations of IDT. Five patients were diagnosed at the IDT stage and two at the DPT stage in the absence of demonstrable specific IgE. Six patients were diagnosed with non-immediate reactions, two on IDT alone and four following IDT and DPT. CONCLUSION: The new PPL and MDM determinants offer enhanced sensitivity when evaluating ß-lactam hypersensitivity; however, there are limitations to the current testing regimens. The UK would benefit from local guidelines, which incorporate the new reagents and acknowledge the high amoxicillin prescription rate and the relatively lower specialist-to-patient ratio in this country.