bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test–retest reliability of the oxygen uptake efficiency slope in surgical patients
Authors: Phypers B. J. , Robiony‐Rogers D. , Pickering R. M. , Garden A. L. 
Published: June 2011

SummaryThe oxygen uptake efficiency slope is a measure of cardiopulmonary fitness, that can be obtained from a sub‐maximal cardiopulmonary exercise test. It has been evaluated in medical patients but its reliability in surgical populations remains uncertain. We conducted a test–retest study with the aim of establishing the reliability of the oxygen uptake efficiency slope in relation to that of the anaerobic threshold and peak oxygen uptake, in general surgical patients. Twenty‐six patients over 60 years old completed two symptom‐limited, incremental cycle ergometry tests within 7 days. The mean (SD) anaerobic threshold was 13.0 (3.0) mlO2.kg−1.min−1. There were no significant differences between mean test and retest values of anaerobic threshold (p = 0.50), peak oxygen uptake (p = 0.76) or oxygen uptake efficiency slope (p = 0.42). Reliability coefficients (95% CI) for the anaerobic threshold, oxygen uptake efficiency slope and peak oxygen uptake were 66.7% (45.3–87.9%), 89.0% (81.0–96.9%) and 91.7% (85.7–97.8%), respectively. The oxygen uptake efficiency slope was determined easily in all patients and found to have excellent reliability. Its clinical utility in determining pre‐operative fitness warrants further evaluation.
Comparison of the manoeuvrability and ease of use of the Ambu aScope and Olympus re‐usable fibrescope in a manikin*
Authors: Vijayakumar M. , Clarke A. , Wilkes A. R. , Goodwin N. , Hodzovic I. 
Published: June 2011

SummaryIn this study, we compared the manoeuvrability and ease of use of the single‐use Ambu aScope and Olympus re‐usable fibrescope in a manikin set to simulate difficult fibrescope placement. A total of 75 anaesthetists took part in this randomised crossover non‐inferiority study. We recorded the time to task completion, tip surface collision count and participants’ impression of ease of use. For the Ambu aScope and Olympus fibrescope, the mean (SD) first attempt time to task completion was 63 (31) s and 53 (23) s, respectively (95% CI of the difference 3–17 s), p = 0.008. This rejected the null hypothesis of a difference of > 30 s. The mean (SD) number of tip surface collisions was 2.7 (1.9) and 2.5 (1.8), respectively, (95% CI of the difference −0.4 to 0.7) p = 0.56. However, the participants found the Olympus easier to use (p < 0.001). Mean (SD) visual analogue scores for the perceived ease of use (0 mm = extremely difficult and 100 mm = extremely easy) were 65 (18) mm and 77 (14) mm for the Ambu aScope and Olympus scopes, respectively. This study found that the single‐use Ambu aScope is as easy to manoeuvre as the Olympus re‐usable fibrescope. This single‐use device appears to be an acceptable alternative to the re‐usable fibrescope.
Addition of clonidine to a continuous patient‐controlled epidural infusion of low‐concentration levobupivacaine plus sufentanil in primiparous women during labour
Authors: Bazin M. , Bonnin M. , Storme B. , Bolandard F. , Vernis L. , Lavergne B. , Pereira B. , Bazin J. E. , Dualé C. 
Published: June 2011

SummaryWe studied the potentiation of analgesia for labour by the addition of clonidine to epidural low‐concentration levobupivacaine with sufentanil in a randomised, double‐blinded study. We enrolled primiparous women who were in spontaneous labour. The study solutions, made of 100 ml levobupivacaine 0.0625% plus sufentanil 0.45 μg.ml−1 and either 150 μg clonidine or no clonidine, were used for induction of analgesia, and for its maintenance with self‐administered boluses and a continuous background infusion. The need for additional epidural boluses during labour was lower and analgesia and maternal satisfaction were better in the clonidine (n = 57) than in the control group (n = 58). Blood pressure was lower and the rate of instrumental delivery higher in the clonidine group. Clonidine (1.36 μg.ml−1) added to the epidural solution of low‐concentration levobupivacaine improves the quality of analgesia. The relevance of the haemodynamic effects should be explored in larger validation studies.
The Difficult Airway Society ‘ADEPT’ Guidance on selecting airway devices: the basis of a strategy for equipment evaluation
Authors: Pandit J. J. , Popat M. T. , Cook T. M. , Wilkes A. R. , Groom P. , Cooke H. , Kapila A. , O’Sullivan E. 
Published: June 2011

SummaryFaced with the concern that an increasing number of airway management devices were being introduced into clinical practice with little or no prior evidence of their clinical efficacy or safety, the Difficult Airway Society formed a working party (Airway Device Evaluation Project Team) to establish a process by which the airway management community within the profession could itself lead a process of formal device/equipment evaluation. Although there are several national and international regulations governing which products can come on to the market and be legitimately sold, there has hitherto been no formal professional guidance relating to how products should be selected (i.e. purchased). The Airway Device Evaluation Project Team’s first task was to formulate such advice, emphasising evidence‐based principles. Team discussions led to a definition of the minimum level of evidence needed to make a pragmatic decision about the purchase or selection of an airway device. The Team concluded that this definition should form the basis of a professional standard, guiding those with responsibility for selecting airway devices. We describe how widespread adoption of this professional standard can act as a driver to create an infrastructure in which the required evidence can be obtained. Essential elements are that: (i) the Difficult Airway Society facilitates a coherent national network of research‐active units; and (ii) individual anaesthetists in hospital trusts play a more active role in local purchasing decisions, applying the relevant evidence and communicating their purchasing decisions to the Difficult Airway Society.
A double‐blind randomised comparison of intravenous patient‐controlled remifentanil with intramuscular pethidine for labour analgesia*
Authors: Ng T. K. T. , Cheng B. C. P. , Chan W. S. , Lam K. K. , Chan M. T. V. 
Published: June 2011

SummaryIn a prospective, double‐blind, randomised controlled trial, we compared the efficacy of patient‐controlled analgesia using remifentanil (25–30 μg per bolus) with intramuscular pethidine (50–75 mg) for labour analgesia in 69 parturients. Parturients receiving patient‐controlled analgesia reported less pain than those receiving intramuscular pethidine throughout the study period (p < 0.001), with maximal reduction in visual analogue pain score at 2 h after commencement of analgesia (mean (SD) 20 (17) in the patient‐controlled analgesia group and 36 (22) in the intramuscular pethidine group. The median (95% CI) time to the first request for rescue analgesics was significantly longer with patient‐controlled analgesia (8.0 (6.8–9.2) h) compared with intramuscular pethidine (4.9 (3.8–5.4) h, p < 0.001). Maternal satisfaction scores were also higher with remifentanil compared with intramuscular pethidine (p= 0.001). There was no report of sedation, aponea or oxygen desaturation in either group, and Apgar scores were similar between groups. We conclude that patient‐controlled analgesia with remifentanil provides better labour analgesia and maternal satisfaction than intramuscular pethidine. At this dose, maternal and fetal side effects were uncommon.
High dose methotrexate chemotherapy: pharmacokinetics, folate and toxicity in osteosarcoma patients
Authors: Holmboe Laila , Andersen Anders M. , Mørkrid Lars , Slørdal Lars , Hall Kirsten Sundby 
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• High dose methotrexate (HD MTX) is generally well tolerated, although unpredictable acute toxicities occur frequently.• Low overall toxicity in paediatric patients and increased liver toxicity in adults has been reported, but there are no reports addressing the relationship between acute liver toxicity and gender in patients treated with HD MTX.• Previous studies in animals suggested involvement of the 7‐hydroxy‐methotrexate metabolite in acute liver toxicity, but this has not been investigated in humans and the aetiology of acute liver toxicity remains unclear.WHAT THIS STUDY ADDS• Survival has increased dramatically over the past decades for patients with malignancies such as osteosarcoma and since these patients are frequently children or adolescents at the time of high dose methotrexate, identification of risk factors for toxicity increases the possibility for tailoring treatment.• Our study presents a detailed analysis of acute toxicity, folate concentrations and pharmacokinetics of both methotrexate and its major extracellular metabolite 7‐hydroxy‐methotrexate and identifies several factors that are highly correlated with acute liver toxicity.AIMSTo investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy.METHODSMTX and its major extracellular metabolite 7‐OH‐MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma patients (288 cycles) and AUC (area under the blood concentration–time curve) was calculated. Pretreatment concentrations of folate in serum (S) and erythrocytes (ER) were determined. Hepatic, renal and haematological toxicities, assessed by routine laboratory parameters, as well as mucositis were graded according to National Cancer Institute Common Terminology Criteria for adverse events (CTCAE v.3.0). Dermatitis and pleuritis were reported as occurred or not.RESULTSS‐ and ER‐folate pretreatment concentrations increased significantly with increasing number of HD MTX cycles (P < 0.001). ER‐folate pretreatment concentrations were higher among males (median 610 nmol l−1, 95% CI 550, 680) compared with females (median 465 nmol l−1, 95% CI 430, 520, P < 0.001), but showed no correlation with MTX or 7‐OH‐MTX pharmacokinetics. We found correlations between alanine aminotransferase peak concentration (ALATmax) and clearance of MTX (P < 0.001), gender (P < 0.001), age (P < 0.001) and 7‐OH‐MTX concentrations (P < 0.001), the latter being the main factor influencing ALATmax.CONCLUSIONOur results suggest that 7‐OH‐MTX is involved in the development of HD MTX hepatic toxicity and that young female patients are most affected.
Interferon-α stimulates TRAIL expression in human keratinocytes and peripheral blood mononuclear cells: implications for the pathogenesis of cutaneous lupus erythematosus
Authors: Zahn S. , Rehkämper C. , Ferring-Schmitt S. , Bieber T. , Tüting T. , Wenzel J. 
Published: June 2011

Summary
Background The tumour necrosis factor-related apoptosis-inducing ligand TRAIL has been shown to participate in the pathogenesis of systemic lupus erythematosus (SLE). The accumulation of apoptotic cell debris has been hypothesized to induce this autoimmune inflammation, and TRAIL may trigger this programmed cell death. Furthermore, TRAIL is among the interferon (IFN)-regulated genes which are typically expressed in the peripheral blood of patients with acute SLE.
Objectives As an inappropriate activation of the type I IFN system plays an important role in both SLE and cutaneous lupus erythematosus (CLE) subsets, we hypothesized that TRAIL might also participate in the pathogenesis of CLE.
Methods Immunohistochemistry and immunofluorescence analyses were used to identify and localize TRAIL-expressing cells in CLE skin specimens. TRAIL expression in peripheral blood mononuclear cells (PBMC) isolated from patients with CLE was measured by flow cytometry. The impact of IFN-α treatment on TRAIL expression by keratinocytes and PBMC was evaluated by reverse transcription–polymerase chain reaction and flow cytometry.
Results Keratinocytes are beside CD11c+ and BDCA2+ dendritic cells the major TRAIL-expressing cells in CLE lesions. TRAIL is upregulated on the surface of circulating CD11c+ PBMC isolated from patients with CLE. Treatment of keratinocytes and PBMC with recombinant IFN-α strongly enhances TRAIL expression by these cells. The proapoptotic TRAIL receptor R1 is expressed by keratinocytes in CLE skin lesions.
Conclusions TRAIL is strongly expressed in the skin and the blood of patients with CLE and may trigger the apoptotic death of kerationcytes in CLE via the TRAIL receptor R1. An IFN-α-induced TRAIL expression may in this way participate in the pathogenesis of CLE.
Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis
Authors: Yayli S. , Pelivani N. , Beltraminelli H. , Wirthmüller U. , Beleznay Z. , Horn M. , Borradori L. 
Published: June 2011

Summary
Background Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the skin associated with IgG autoantibodies to BP180 and BP230, while mucous membrane pemphigoid (MMP) comprises a heterogeneous group of autoimmune blistering diseases characterized by a predominant mucous membrane involvement and scarring tendency associated with an autoantibody response to various autoantigens, including BP180. While the pathogenicity of IgG autoantibodies to BP180 has been demonstrated in BP, the role of IgE autoantibodies in mediating tissue damage in BP and MMP is unclear.
Objectives To assess the presence of tissue-bound IgE in patients with BP and MMP, and their correlation with distinct clinical features.
Methods In this retrospective study, we assessed the presence of IgE deposits as detected by direct immunofluorescence microscopy of skin biopsy specimens obtained from 44 and 13 patients with a new diagnosis of BP and MMP, respectively. Distinct clinical features at time of diagnosis, such as itch, urticarial papules and plaques and eczematous lesions, were noted.
Results In 18 of 44 (41%) patients with BP linear deposits of IgE of variable intensity were detectable along the dermoepidermal junction. In 14 (32%) of the cases, IgE deposits were found concomitantly with IgG and C3. In two (5%) patients, diagnosis of BP was based on the isolated detection of IgE together with consistent clinicopathological features. Nine of 13 (69%) patients with MMP also exhibited linear IgE deposits, including one case with isolated linear IgE deposits. Patients with BP with tissue-bound IgE deposits had clinically significant urticarial papules and plaques when compared with patients with BP without IgE deposits.
Conclusions Our findings indicate that demonstration of tissue-bound IgE deposits provides an additional useful criterion for diagnosis of BP and MMP in some patients. Prospective studies are needed to better correlate the presence of tissue-bound and circulating IgE autoantibodies and their specificity with distinct clinical features and course of BP and MMP.
Factors in the surgical management of primary eccrine porocarcinoma: prognostic histological factors can guide the surgical procedure
Authors: Belin E. , Ezzedine K. , Stanislas S. , Lalanne N. , Beylot-Barry M. , Taieb A. , Vergier B. , Jouary T. 
Published: June 2011

Summary
Background Primary eccrine porocarcinoma is a rare cutaneous neoplasm and there is no consensus concerning its surgical management.
Objectives To conduct a retrospective analysis of all the cases of eccrine porocarcinoma seen in our hospital in order to identify prognostic factors.
Methods Clinical data were retrieved from the patients’ files. Each histological sample was reviewed by the pathologist and classified into three eccrine porocarcinoma subtypes: ‘infiltrative’, ‘pushing’ and ‘pagetoid’ eccrine porocarcinoma, according to Robson’s criteria. Statistical methods were used to estimate the recurrence risk.
Results Twenty-four patients were included. The surgical margins realized were ≥ 2 cm or &lt; 2 cm in six and 13 patients, respectively, and slow Mohs procedure was performed in two patients. Ten, seven and two patients presented with ‘infiltrative’, ‘pushing’ or ‘pagetoid’ eccrine porocarcinoma, respectively. Eight patients (of 23) experienced recurrences (35%). The recurrence risk was linked to the histological subtype: two out of two pagetoid eccrine porocarcinoma, four out of 10 ‘infiltrative’ and none of seven ‘pushing’ eccrine porocarcinoma recurred (P =0·026). The recurrence risk was not associated with epidermal growth factor receptor status, nor the margin realized.
Conclusions The recurrence risk of ‘pushing’ eccrine porocarcinoma is significantly lower than for ‘infiltrative’ eccrine porocarcinoma. Based on these considerations, a decisional algorithm might be proposed: first step, excisional biopsy of the primary eccrine porocarcinoma and identification of the histological subtype; second step, infiltrative or pagetoid porocarcinoma should be excised with an additional modified micrographic Mohs procedure, while no additional surgery is needed for ‘pushing’ eccrine porocarcinoma if the first excisional biopsy is complete. Although demonstrated in a limited case series, the histological subtype might guide the surgical management of primary eccrine porocarcinoma.
CXCR3 ligands promote expression of functional indoleamine 2,3-dioxygenase in basal cell carcinoma keratinocytes
Authors: Lo B.K.K. , Jalili R.B. , Zloty D. , Ghahary A. , Cowan B. , Dutz J.P. , Carr N. , Shapiro J. , McElwee K.J. 
Published: June 2011

SummaryBackground Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Studies suggest that BCCs exhibit immunoprotection, similar to other keratinocyte carcinomas, although the mechanisms of defence have not been defined.Objectives To examine if indoleamine 2,3-dioxygenase (IDO), an immune privilege-associated enzyme, would be expressed in BCC, regulated in part by CXCR3.Methods We analysed the expression and function of IDO in human BCC (hBCC) tissues using nonlesional skin epithelial (NL) tissues as a control.Results Quantitative real-time reverse transcription–polymerase chain reaction (qPCR) revealed significant upregulation of IDO1 and IDO2 (12·5- and 19·14-fold change, respectively) in nodular hBCCs as compared with NL tissues. Immunohistochemistry showed that IDO colocalized with keratin 17, a BCC keratinocyte marker, in hBCC tissues. Western blot identified a full-length IDO (42 kDa) product and a splice variant (∼30 kDa) in BCC tissues. Kynurenine assays and qPCR were conducted to determine IDO enzymatic activity in hBCCs in vitro with CXCL11 supplementation, which has previously been shown to be required for the tumour cell growth. Addition of CXCL11 upregulated IDO2 and increased l-kynurenine concentration in a dose-dependent manner in hBCCs while normal primary keratinocytes exhibited no response.Conclusions The expression of IDO at both mRNA and protein levels in hBCC tissues, the upregulation of IDO2 and the IDO-mediated l-kynurenine production in hBCCs with CXCL11 treatment suggest that functional IDO is synthesized by hBCC tumours and may be used as a method of immunoprotection during tumorigenesis. Also, IDO enzymatic activity may be modulated by CXCR3/CXCL11 signalling in BCCs.
Functional analysis of splice site mutations in the human hairless (HR) gene using a minigene assay
Authors: Refke M. , Pasternack S.M. , Fiebig B. , Wenzel S. , Ishorst N. , Ludwig M. , Nöthen M.M. , Seyger M.M. , Hamel B.C. , Betz R.C. 
Published: June 2011

SummaryBackground Congenital atrichia is a rare autosomal recessive form of isolated alopecia which is caused by mutations in the human hairless (HR) gene. Patients are born with normal hair that is shed almost completely and irreversibly during the first weeks of life.Objectives To investigate the molecular genetic basis of congenital atrichia in two patients, and to analyse the functional consequences of one newly identified and all seven previously identified HR splice site mutations using a minigene assay.Methods Molecular analysis of the HR gene was performed by direct DNA sequencing. To analyse the functional consequences of the splice site mutations, the respective sequences were cloned into a vector which allows directed splicing. After transfection of COS7 cells, isolation of RNA and cDNA synthesis, sequencing was performed to analyse the products.Results Two novel mutations were identified: an insertion in exon 2 (c.485insT; p.C162LfsX17), and a splice site mutation (c.2847–1G&gt;A). In vitro analysis revealed aberrant splicing for all eight of the investigated HR splice site mutations. Comparison with the results of two biocomputational programs (neural network splice server and CRYP-SKIP) and calculation of consensus values revealed that the predictions of these two programs were consistent in only five and two of the eight mutations, respectively.Conclusions This is the first report to analyse the consequences of HR splice site mutations using a cell-based in vitro assay. The results highlight the importance of performing splicing experiments to clarify the consequences of putative splice site mutations.
Nodular lesions arising in a large congenital melanocytic naevus in a newborn with eruptive disseminated Spitz naevi
Authors: Feito-Rodríguez M. , de Lucas-Laguna R. , Bastian B.C. , LeBoit P. , González-Beato M.J. , López-Gutiérrez J.C. , Requena L. , Pizarro A. 
Published: June 2011

Summary
Congenital malignant melanoma within a pre-existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark-brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome-shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign proliferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi.
Severe acquired anaemia in Africa: new concepts
Authors: van Hensbroek Michael B. , Jonker Femkje , Bates Imelda 
Published: June 2011

SummarySevere anaemia is common in Africa. It has a high mortality and particularly affects young children and pregnant women. Recent research provides new insights into the mechanisms and causes of severe acquired anaemia and overturns accepted dogma. Deficiencies of vitamin B12 and vitamin A, but not of iron or folic acid, are associated with severe anaemia. Bacterial infections and, in very young children, hookworm infections are also common in severe anaemia. Irrespective of the aetiology, the mechanism causing severe anaemia is often red cell production failure. Severe anaemia in Africa is therefore a complex multi‐factorial syndrome, which, even in an individual patient, is unlikely to be amenable to a single intervention. Policies and practices concerning anaemia diagnosis, treatment and prevention need to be substantially revised if we are to make a significant impact on the huge burden of severe anaemia in Africa.