Association of Anaesthetists guidelines: cell salvage for peri-operative blood conservation 2018.

The use of cell salvage is recommended when it can be expected to reduce the likelihood of allogeneic (donor) red cell transfusion and/or severe postoperative anaemia. We support and encourage a continued increase in the appropriate use of peri-operative cell salvage and we recommend that it should be available for immediate use 24 h a day in any hospital undertaking surgery where blood loss is a recognised potential complication (other than minor/day case procedures).

Cognitive constraints influence an understanding of life-cycle change.

We investigated children's (n = 120; 3- to 11-year-olds) and adults' (n = 18) reasoning about life-cycle changes in biological organisms by examining their endorsements of four different patterns of life-span changes. Participants were presented with two separate tasks: (a) judging possible adult versions of a juvenile animal and (b) judging possible juvenile versions of an adult animal. The stimuli enabled us to examine the endorsement of four different patterns of change: identical growth, natural growth, dramatic change, and speciation. The results suggest that endorsement of the different patterns is influenced by age and familiarity. Young children and individuals confronted with unfamiliar organisms often endorsed an identical growth that emphasizes the stability of features over the life span and between parents and offspring. The results are interpreted as supporting the idea that cognitive constraints influence individuals' reasoning about biological change and that the influence of these constraints is most notable when individuals are young or are presented with unfamiliar biological organisms.

High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIM: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed. RESULTS: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m2 (21.4-28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies. CONCLUSION: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.

Did she mean to do it? Acquiring a folk theory of intentionality.

The ability to both identify and explain others' intentional acts is fundamental for successful social interaction. In two cross-sectional studies, we investigated 3- to 9-year-olds' (n=148) understanding of the folk concept of intentionality, using three types of intentionality measures. The relationship between this type of reasoning and false belief and interpretive mind understanding was also examined. Judgment of the appropriateness of an explanation was based on adult responses (n=20). Overall, the results indicated that the ability to both identify and appropriately explain a range of intentional acts does not fully emerge until 7 years of age or later. The pattern of explanations revealed the gradual development of a folk concept of intentionality. Preschool- and early school-age children focused on the protagonists' desires and actions, whereas 8- and 9-year-olds and adults were more likely to reference the protagonists' awareness and skills.

Trans-bonded pairs of E-cadherin exhibit a remarkable hierarchy of mechanical strengths.

Classical cadherins are primary mediators of calcium-dependent cell interactions in multicellular organisms. Organized in five tandemly repeated E-cadherin (EC) modules, the extracellular segments of these membrane-spanning glycoproteins interact homophilically between opposing cells to create highly regulated patterns of attachment stabilized by cytoskeletal elements inside the cells. Despite many structural and functional studies, a significant controversy exists in regard to the organization of cadherin binding in adhesion sites. Supported by considerable evidence, perhaps the most widely held view is that opposing N-terminal EC1-EC2 (EC12) domains form a "zipper" of bonds. However, immobilized on two atomically smooth surfaces and pushed to adhesive contact, opposing cadherins become fully interdigitated and unbind through three discrete jumps comparable with domain dimensions when pulled apart. So the question remains as to whether mechanical adhesion strength emanates solely from interactions between the peripheral N-terminal domains or involves multiple overlapping domains. It is also unclear whether a primary adhesion complex is formed by a single opposing pair of cadherins or whether the complex involves a more complicated network of cis-bonded multimers. To address these questions, we used a special jump/ramp mode of force spectroscopy to test isolated pairwise interactions between recombinant fragments of ECs. Besides the formation of strong trans-bonded dimers, we find a remarkable hierarchy of rupture strengths for bonds between the full five-domain fragments that suggests multiple mechanical functions for cadherins, perhaps providing distinct properties needed for transient-specific recognition as well as stable tissue formation.

A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations.

OBJECTIVE: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. METHODS: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom*, lipid*, colloid*, antifungal agents, and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. RESULTS: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. CONCLUSIONS: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.

Comparison of fluoroquinolone pharmacokinetic parameters after treatment with marbofloxacin, enrofloxacin, and difloxacin in dogs.

Plasma, urine, and skin drug concentrations were determined for dogs (n=12) given five daily oral doses of marbofloxacin (MAR) (2.75 mg/kg), enrofloxacin (ENR) (5.0 mg/kg) or difloxacin (DIF) (5.0 mg/kg). Concentrations of the active metabolite of ENR, ciprofloxacin (CIP), were also determined. The three-period, three-treatment crossover experimental design included a 21-day washout period between treatments. Area under the plasma drug concentration vs. time curve (AUC0-last, microg/mLxh of MAR was greater than for ENR, CIP, ENR/CIP combined, and DIF. Maximum concentration (Cmax) of MAR was greater than ENR, CIP, and DIF. Time of maximum plasma concentration (Tmax) was similar for MAR and DIF; Tmax occurred earlier for ENR and later for CIP. Plasma half-life (t1/2) of MAR was longer than for ENR, CIP, and DIF. Urine concentrations of DIF were less than MAR or ENR/CIP combined, but urine concentrations of MAR and ENR/CIP combined did not differ. DIF skin concentrations were less than the concentrations of MAR or ENR/CIP combined 2 h after dosing, but skin concentrations of MAR and ENR/CIP combined did not differ.

Determination of biotin and folate in infant formula and milk by optical biosensor-based immunoassay.

Biomolecular interaction analysis was evaluated for the automated analysis of biotin- and folate-supplemented infant formulas and milk powders. The technique was configured as a biosensor-based, nonlabeled inhibition immunoassay using monoclonal antibodies raised against analyte-conjugate. Sample extraction conditions were optimized and antibodies were evaluated for cross-reactivity. Performance parameters included a quantitation range of 2-70 ng/mL, recoveries of 86-102%, agreement against assigned reference values for National Institute of Standards and Technology Standard Reference Material 1846, between-laboratory reproducibility relative standard deviation of 9.1% for biotin and 8.1% for folate, respectively, and equivalence against reference microbiological assay methods for both analytes.

Tinea pedis: clinical experience and efficacy of short treatment.

Tinea pedis is the commonest fungal infection in developed countries. Topical therapy is an accepted and successful method for the management of this condition. This has usually involved the application of an antifungal twice or 3 times a day for 3-4 weeks to achieve a cure rate of > or = 80%. Terbinafine, a new antifungal, has been shown in a number of studies to give equally good results when applied once or twice daily for 1-2 weeks. In one study, a cure rate of 78% was achieved in patients with tinea pedis after a single application of 1% terbinafine cream, demonstrating the high potency of this antifungal. Topical terbinafine has also been compared to clotrimazole for the treatment of tinea pedis. Terbinafine 1% cream applied twice daily for 1 week was significantly superior to a 4-week course of clotrimazole 1% cream for treating this common mycosis. Overall, the high efficacy of topical terbinafine in treating tinea pedis following such-short-duration therapy is undoubtedly due to its fungicidal mode of action.

Fungal infections: a survey of laboratory services for diagnosis and treatment.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.

A comparison of terbinafine (Lamisil) 1% cream given for one week with clotrimazole (Canesten) 1% cream given for four weeks, in the treatment of tinea pedis.

Terbinafine (Lamisil) is a synthetic allylamine antifungal which has been shown to be fungicidal against dermatophytes and a number of yeasts and moulds. Topical application of terbinafine 1% cream has been shown to be a highly effective short-duration therapy for dermatophytosis of the skin. The aim of this multicentre, double-blind, parallel-group study was to compare the safety and efficacy of terbinafine 1% cream, applied twice daily for 1 week, with clotrimazole (Canesten) 1% cream, applied twice daily for 4 weeks, in the treatment of tinea pedis. One hundred and seven patients with mycologically proven tinea pedis received 1 week of terbinafine 1% cream, followed by 3 weeks of placebo, and 104 patients received clotrimazole 1% cream for 4 weeks. Mycological cure (negative microscopy and culture) and effective treatment (mycological cure with no or minimal signs and symptoms) were assessed 4 and 6 weeks after commencing therapy. Mycological cure rates were 93.5% for terbinafine and 73.1% for clotrimazole (P = 0.0001) at 4 weeks. Effective treatment rates at 4 weeks were 89.7% for terbinafine and 58.7% for clotrimazole (P = 0.0001), and 89.7% for terbinafine and 73.1% for clotrimazole (P = 0.002) at 6 weeks. The results show that 1 week of terbinafine b.d. is more effective than 4 weeks of clotrimazole b.d., in terms of both mycological cure and effective treatment.

Iron chelator, exopolysaccharide and protease production in Staphylococcus epidermidis: a comparative study of the effects of specific growth rate in biofilm and planktonic culture.

The growth rate of Staphylococcus epidermidis was controlled for populations growing as a biofilm and perfused with supplemented, simple-salts medium. Production of iron chelators, extracellular protease and exopolysaccharide (EPS) by these populations was assessed as a function of specific growth rate and compared to that by planktonic populations grown in the same medium within a chemostat. Perfused biofilms increased their iron chelator and protease production with increasing growth rate. Chemostat populations decreased their production of iron chelators with increasing growth rate, whilst showing much enhanced production of proteases at intermediate growth rates (mu 0.15-0.25 h-1). Production of iron chelator and protease was generally 2-50 times higher by biofilms than by planktonic populations. EPS production was low and relatively unaffected by growth rate for the chemostat cultures (about 0.2 micrograms per unit cell mass) but high for the attached biofilms, particularly at slow growth rates (about 4 micrograms per unit cell mass). EPS production within the biofilms decreased markedly with increasing growth rate. At growth rates of 0.35 h-1 and above, the levels of EPS for biofilms and planktonic populations were equivalent. The results of this study clearly indicate that growth as a biofilm markedly influences extracellular virulence factor production by S. epidermidis.

Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin.

In a multicentre, double-blind, randomized, parallel group study in general practice, 269 patients with clinically diagnosed fungal infection of the skin were treated with either naftifine (Exoderil) or 1% clotrimazole plus 1% hydrocortisone (CHC; Canesten HC) applied twice daily for 4 weeks. Only 115 patients were shown subsequently to have a fungal infection by laboratory tests; the others had inflammatory disease of unknown aetiology. In those with fungal disease, both treatments were equally effective in terms of mycological cure (negative microscopy and culture). Clinical results for all 265 patients showed no clinically identifiable difference between the two preparations in terms of resolution of the disease, indicating that naftifine does have anti-inflammatory activity at least equal to CHC. This study suggests that there is no clinical advantage in treating patients with clinically diagnosed fungal infection of the skin with an antimycotic/corticosteroid combination as opposed to naftifine alone.

Comparison of terbinafine and clotrimazole in treating tinea pedis.

OBJECTIVE: To compare the efficacy and safety of terbinafine 1% cream and clotrimazole 1% cream in the treatment of tinea pedis. DESIGN: Multicentre, double blind parallel group study. SETTING: 32 general practices and one hospital. PATIENTS: 256 patients with mycologically confirmed tinea pedis. Of the 211 patients evaluable, 107 were randomised to terbinafine (75 male, 32 female; mean (range) age 40 (12-81) years) and 104 to clotrimazole (79 male, 25 female; mean (range) age 36 (12-71) years). INTERVENTIONS: Terbinafine 1% cream applied twice daily for one week and inert cream applied twice daily for the next three weeks. Clotrimazole 1% cream applied twice daily for four weeks. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and effective treatment (mycological cure plus no or minimal signs and symptoms) measured at weeks 1, 2, 3, 4, and 6. RESULTS: At week four rates of mycological cure were 93.5% for terbinafine and 73.1% for clotrimazole (p = 0.0001); and at week six 97.2% for terbinafine and 83.7% for clotrimazole (p = 0.001). Rates of effective treatment at week 4 were 89.7% for terbinafine and 58.7% for clotrimazole (p = 0.0001); and 89.7% for terbinafine and 73.1% for clotrimazole (p = 0.002) at week 6. CONCLUSION: These results indicate that a one week course of terbinafine 1% cream is more effective in the treatment of tinea pedis than a four week course of clotrimazole 1% cream, both in terms of mycological cure and effective treatment.

Behavioural evidence for recovery of auditory function in guinea pigs following kanamycin administration.

Deterioration followed by recovery of behavioural absolute threshold and frequency selectivity has been observed in guinea pigs following kanamycin administration of 200 mg/kg body weight daily for 16 days. Deterioration in function consistently follows a high-to-low frequency pattern and recovery generally occurs at the lowest of the high (8-32 kHz) frequencies affected. The degree of recovery is related to the magnitude of the threshold elevation; where large (40-45 dB) elevations occur initially, the process appears to be partial since threshold recovers only to within 5-12 dB of pre-administration levels. In instances where smaller threshold elevations (5-20 dB) take place initially, recovery can sometimes be complete. However, when threshold elevations of over 50 dB occur, no recovery is apparent. Recovery is relatively slow, taking place over periods of up to 100 days post-kanamycin administration. Hair cell counts have established that the threshold elevation which remains in instances of partial recovery is not related to a reduction in hair cell numbers at the light microscope level.

Clotrimazole (Canesten) in the treatment of candidal balanitis in men. With incidental observations on diabetic candidal balanoposthitis.

Clotrimazole 1% (Canesten) cream was used in a trial comprising 138 men with candidal balanitis. Eighty-six (91%) out of 94 men were asymptomatic after seven days and 57 (98%) of 58 men were asymptomatic after three weeks' treatment. After seven days, Candida albicans could no longer be cultured from 86 (90%) of 96 men, nor from 55 (95%) of 58 men three weeks after treatment. Microscopical examination gave varying results. Fifteen (10.9%) of 138 men were found to have diabetes mellitus; this group was significantly older than the non-diabetics. It is concluded that treatment with clotrimazole for seven days is effective in the treatment of candidal balanitis.

Eclectic relaxation therapy.

This paper introduces a new method that is designed to facilitate muscular relaxation, enhance direct sensory reality and increase self-control over mental processes. The procedure consists of six sessions and requires minimal therapist involvement, the therapy being presented in a group setting by tape recordings. The advantages of this technique are suggested and the principles used in its construction are defined.