bluuebunny/crossref_metadata_2025 huggingface dataset:
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

In 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

We 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

Faced 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

In 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.

AIMS

To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy.

METHODS

MTX 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.

RESULTS

S‐ 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.

CONCLUSION

Our 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

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

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

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 < 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

Background 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

Background 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>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

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

Severe 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.
Palliative care: what approaches are suitable in developing countries?
Authors: Ddungu Henry
Published: June 2011

The enormous burden of life‐threatening illnesses, including cancer, human immunodeficiency virus infection, and others, such as sickle cell disease, associated with physical and psychosocial suffering explains the illustrious need for palliative care in developing countries. Despite the demonstrated need, current provision of palliative care in Africa is at best limited, and at worst non‐existent. Access to essential pain medicines, particularly oral morphine, for control of pain is extremely limited and far below the global mean. There is a general lack of government policies that recognize palliative care as an essential component of health care and there is inadequate training for both health care professionals and the general public about palliative care. A public health strategy, as recommended by the World Health Organization (WHO), offers the best approach for translating knowledge and skills into evidence‐based, cost‐effective interventions that can reach everyone in need of palliative care in developing countries.
Chelation treatment in sickle‐cell‐anaemia: much ado about nothing?
Authors: Lucania Gaetano , Vitrano Angela , Filosa Aldo , Maggio Aurelio
Published: June 2011

Blood transfusions may prevent and treat serious complications related to sickle‐cell disease (SCD) when performed according to specific guidelines. However, blood transfusion requirements in SCD inevitably lead to increased body iron burden. An adequate chelation treatment may prevent complications and reduce morbidity and mortality. This review evaluates the effectiveness, safety and costs of chelation treatment. The included trials were examined according to the recommendations of the American College of Cardiology (ACC) and the American Heart Association (AHA). Overall, 14 trials and a total of 502 patients with SCD were included in this review. Deferoxamine alone (s.c. or i.v.), deferiprone alone or versus deferoxamine, deferasirox versus deferoxamine and combined treatment with deferoxamine plus deferiprone were included and evaluated in the analysis. Only two randomized clinical trials have been reported. The results of this analysis suggest that use of chelation treatment in SCD to date has been based on little efficacy and safety evidence, although it is widely recommended and practised. The cost/benefit ratio has not been fully explored. Further research with larger randomized clinical trials needs to be performed.
Genetic strategies for the treatment of sickle cell anaemia
Authors: Mansilla‐Soto Jorge , Rivière Isabelle , Sadelain Michel
Published: June 2011

Sickle cell anaemia is a severe inherited blood disorder for which there is presently no curative therapy other than allogeneic haematopoietic stem cell (HSC) transplantation. This therapeutic option, however, is not available to most patients because of the lack of a matched related donor. Different genetic strategies aiming to treat the anaemia and prevent sickling are under investigation. They include strategies to transfer a regulated globin gene in autologous HSCs–the most developed approach, which is about to undergo clinical evaluation–, and strategies to either restore endogenous HBG expression, repair or eliminate HBBS mutant transcripts, or correct the sickle mutation in HSCs or induced pluripotent stem cells. Their common ultimate goals are to afford therapeutic levels of HbA or HbF in the erythroid progeny of autologous HSCs (sufficient to prevent pathological sickling) and engraft the genetically modified HSCs with minimal short‐term toxicity (primarily caused by the conditioning regimen) and long‐term toxicity (primarily caused by genotoxicity). We discuss here the status of application of these technologies, outlining recent advances and the hurdles that lay ahead.
The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non‐Hodgkin lymphoma of distinct histological origin
Authors: Czuczman Myron S. , Vose Julie M. , Witzig Thomas E. , Zinzani Pier L. , Buckstein Rena , Polikoff Jonathan , Li Ju , Pietronigro Dennis , Ervin‐Haynes Annetti , Reeder Craig B.
Published: June 2011

Transformed lymphoma (TL) represents a heterogeneous group of lymphomas with an aggressive course and poor prognosis. We assessed the clinical benefit of single‐agent lenalidomide based on histological origin, including transformed follicular lymphoma (tFL) and transformed chronic lymphocytic leukaemia/small lymphocytic lymphoma (tCLL/SLL). Our analysis included 33 patients with TL. Patients received lenalidomide at a median dose of 25 mg/d. The overall response rate (ORR) was 46%, with a median response duration of 12·8 months after a median follow‐up of 5·6 months. Median progression‐free survival was 5·4 months. Among patients with tFL, ORR was 57%, with a median response duration of 12·8 months. None of the patients with tCLL/SLL responded to lenalidomide monotherapy. The most common grade 3/4 adverse events were reversible myelosuppression. Our results suggest that the original lymphoma histology (i.e. FL) in TL patients may potentially be associated with response to salvage lenalidomide monotherapy.
Cross‐border marriage and disparities in early childhood development in a population‐based birth cohort study: the mediation of the home environment
Authors: Wu J. C.‐L. , Bradley R. H. , Chiang T.‐L.
Published: June 2011

Background Taiwan has experienced a large influx of cross‐border marriage migrants in recent years. The majority have been women in their childbearing ages and have come from countries with lower average standards of living than Taiwan. This trend has changed the ethnic composition of children who live in Taiwan, and it has generated considerable social concern over the future health status of Taiwan's citizens. This study aimed to examine: (1) whether there are disparities in development between children reared in families characterized by cross‐border marriages and children reared in families with two Taiwanese‐born parents; and (2) whether the quality of home environment explains the group differences in early childhood development.

Methods Data came from the Taiwan Birth Cohort Study. A total of 19 499 participants who completed 6‐month, 18‐month and 3‐year surveys were included for analysis. Cross‐border marriage status was defined by mother's original nationality and categorized into three broad groups: Taiwanese‐born, Chinese cross‐border and South‐East Asian (SEA) cross‐border. Early childhood development was measured at age 3 years, and covered the domains of gross motor, fine motor, language and socio‐emotional competence. Hierarchical linear regressions were used to examine the mediation effects of the home environment.

Results Children of Chinese and SEA cross‐border groups scored lower in fine motor, language and socio‐emotional competence than those of their Taiwanese‐born counterpart at age 3 years. Chinese–Taiwanese group differences in all three developmental domains became insignificant after the addition of home environment, while SEA–Taiwanese group differences in fine motor and language development remained, yet were noticeably reduced. The mediation of home environment was further confirmed using the Sobel test.

Conclusions Home environment plays a central role in reducing the disparities in developmental outcomes among children of different marriage groups. Interventions should be directed towards enhancing the quality of early home environment for children reared in families of cross‐border marriages.
Loss of balance between T helper type 17 and regulatory T cells in chronic human immunodeficiency virus infection
Authors: Li D , Chen J , Jia M , Hong K , Ruan Y , Liang H , Liu S , Zhang X , Zhao H , Peng H , Ma P , Shao Y
Published: June 2011

The aim of this study is to characterize the changes of CD4+CD25highforkhead box P3 (FoxP3+) regulatory T cells (Treg), interleukin (IL)-17 secreting T helper type 17 (Th17) cell frequencies and the balance of these two subsets in a cohort of chronic human immunodeficiency virus type 1 (HIV-1)-infected patients in China. A total of 115 untreated chronic HIV-infected individuals and 32 healthy donors were recruited in this study. Peripheral blood mononuclear cells were isolated from ethylenediamine tetracetic acid (EDTA) anti-coagulated fresh whole blood and stained to characterize the frequencies of Treg and Th17. Of a total 115 patients, 42 individuals including 10 elite controllers were followed-up for more than 1 year, and changes of Treg and Th17 frequencies were analysed over time. The continuous loss of Th17 cells was accompanied by a concomitant rise in the frequency of Treg cells, resulting in a loss of Th17/Treg balance during the progressive HIV infection. Meanwhile, the Treg levels, Th17 levels and Th17/Treg ratios of the elite controller group were comparable to those of the HIV-1 negative controls in the follow-up study. Additionally, we demonstrated that loss of balance between Th17 and Treg is associated with an earlier CD4 T cell decline during the course of HIV infection. Our results indicate that a loss of immune-balance of Th17 to Treg during HIV-1 disease progression and the persistence of such an immune-balance in the elite controllers may have a critical role in HIV-1 infection and further shed new light into understanding the pathogenesis of HIV-1.
Stimulation of dendritic cells withHelicobacter pylorivacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1
Authors: Kim J M , Kim J S , Yoo D Y , Ko S H , Kim N , Kim H , Kim Y-J
Published: June 2011

Helicobacter pylori induces an infiltration of dendritic cells (DCs) into the infected gastric mucosa. Although DCs play an important role in the regulation of inflammation, the effects of H. pylori vacuolating cytotoxin (VacA) on DC maturation process have not yet been elucidated. The role of VacA in DC maturation following co-exposure to Escherichia coli lipopolysaccharide (LPS) was investigated. The treatment of immature DCs with LPS up-regulated the expression of surface molecules [e.g. CD40, CD80, CD86 and major histocompatibility complex (MHC) class II], as well as the production of cytokines [e.g. interleukin (IL)-1β, IL-12p70 and tumour necrosis gactor (TNF)-α] compared with those of unstimulated controls. Co-stimulation with H. pylori VacA significantly reduced the up-regulated DC maturation markers induced by LPS. In addition, VacA sustained the immature state of DCs with high endocytosis and low migratory capacity. The LPS-induced down-regulation of E2F1 expression in DCs was recovered by co-stimulation with VacA. Moreover, suppression of E2F1 by small interfering RNA resulted in a significant recovery of the inhibited DC maturation by VacA. In contrast, VacA did not affect nuclear factor (NF)-κB responses to LPS and the NF-κB signal was not associated with VacA-induced inhibition of DC maturation. These results suggest that the exposure of DCs to H. pylori VacA negatively regulates DC maturation via the restoration of E2F1. The immunomodulatory action of VacA on DCs may contribute to the ability of VacA-producing H. pylori to establish a persistent infection in the gastric mucosa.
Iron administration reduces airway hyperreactivity and eosinophilia in a mouse model of allergic asthma
Authors: Maazi H , Shirinbak S , Bloksma N , Nawijn M C , van Oosterhout A J M
Published: June 2011

The prevalence of allergic diseases has increased dramatically during the last four decades and is paralleled by a striking increase in iron intake by infants in affluent societies. Several studies have suggested a link between increased iron intake and the marked increase in prevalence of allergic diseases. We hypothesized that the increased iron intake by infants offers an explanation for the increased prevalence of allergic disease in industrialized societies during the past four decades. A well-established mouse model of ovalbumin (OVA)-driven allergic asthma was used to test the effects of differences in iron intake and systemic iron levels on the manifestations of allergic asthma. Surprisingly, iron supplementation resulted in a significant decrease in airway eosinophilia, while systemic iron injections lead to a significant suppression of both allergen-induced airway eosinophilia and hyperreactivity compared to placebo. In contrast, mice fed on an iron-deprived diet did not show any difference in developing experimentally induced allergic asthma when compared to those fed on an iron-sufficient control diet. In contrast to our hypothesis, airway manifestations of allergic asthma are suppressed by both increased levels of iron intake and systemic iron administrations in the mouse model.
The relationship between fat depot‐specific preadipocyte differentiation and metabolic syndrome in obese women
Authors: Park Hyun Tae , Lee Eun Sil , Cheon Yong‐Pil , Lee Dong Ryul , Yang Kyung‐Sook , Kim Young Tae , Hur Jun Young , Kim Sun Haeng , Lee Kyu Wan , Kim Tak
Published: June 2011

Objective  Obesity is strongly associated with metabolic syndrome, but not all obese individuals display a clustering of metabolic risk factors. Recent studies have shown that in vitro subcutaneous (SC)‐preadipocyte differentiation is negatively associated with obesity. These results suggest that impaired adipogenesis is an important factor linking obesity to metabolic disorders. We examined whether in vitro preadipocyte differentiation is associated with metabolic syndrome, independent of obesity.

Design/patients/measurements  Paired adipose tissue samples were obtained from the 13 nonobese women and the 65 obese women. The CD34+/CD31− cells were isolated from the stromal‐vascular fraction of both SC and omental (OM) fat depots by immune magnetic separation, and the subset was cultured with a differentiation cocktail. Then, we analysed the relationship between the degree of preadipocyte differentiation and metabolic factors.

Results  Obese women without metabolic syndrome (n = 37) had significantly higher SC‐preadipocyte differentiation than equally obese women with metabolic syndrome (n = 28); however, OM‐preadipocyte differentiation was similar in both groups. SC‐preadipocyte differentiation was strongly correlated with triglycerides, HDL cholesterol, homoeostasis model assessment of insulin resistance and OM‐adipocyte size. However, OM‐preadipocyte differentiation was not correlated with any of these parameters.

Conclusions  This study identified that SC‐preadipocyte differentiation is associated with metabolic syndrome independent of obesity, whereas OM‐preadipocyte differentiation is not. These findings suggest that, in the setting of obesity, an enhanced adipogenic capacity of SC depots could be protective for metabolic syndrome. Our data underscores an interaction between adipose tissue homoeostasis and metabolic disorder.
Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader–Willi syndrome
Authors: Radicioni A. F. , Di Giorgio G. , Grugni G. , Cuttini M. , Losacco V. , Anzuini A. , Spera S. , Marzano C. , Lenzi A. , Cappa M. , Crinò A.
Published: June 2011

Background  Hypogonadism in Prader–Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear.

Objectives  To investigate the aetiology of hypothalamic–pituitary–gonadal axis dysfunction in PWS males.

Methods  Clinical examination and blood sampling for luteinizing hormone (LH), follicle‐stimulating hormone (FSH), testosterone, inhibin B and sexhormone–binding globulin (SHBG) were performed in 34 PWS patients, age 5·1–42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years.

Results  Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near‐significantly lower LH, testosterone, SHBG, inhibin B and higher FSH.

Conclusion  PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH‐inhibin B axis and central origin for LH‐T axis).
Polymorphisms of the UCP2 gene are associated with body fat distribution and risk of abdominal obesity in Spanish population
Authors: Martinez‐Hervas Sergio , Mansego Maria L. , de Marco Griselda , Martinez Fernando , Alonso Mónica P. , Morcillo Sonsoles , Rojo‐Martinez Gemma , Real Jose T. , Ascaso Juan F. , Redon Josep , Martin Escudero Juan C. , Soriguer Federico , Chaves Felipe J.
Published: June 2011

Eur J Clin Invest 2011

Background  Increased accumulation of fat results from an imbalance between energy expenditure and intake, being modulated by different environmental and genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins able to spend energy generating heat. Therefore, variations in these genes are good candidates as potential modulators of body fat accumulation. Our aim was to investigate the possible association of genetic variations of the gene codifying the UCP2 protein with obesity and fat distribution.

Design  We performed a cross‐sectional study in 2367 individuals from two population‐based studies from different regions of Spain. The Hortega Study included 1436 individuals (693 women) 21–85 years old, and the Pizarra Study included 931 individuals (584 women) 18–65 years old. We evaluated three polymorphisms of the UCP2 gene.

Results  The TT genotype of the rs660339 polymorphism and the AA genotype of the rs659366 polymorphism of the UCP2 gene were significantly associated with higher waist circumference in the Hortega Study. Furthermore, subjects carrying both genotypes (TT+AA) also showed higher central adiposity compared with other genotypes. This association was also present in the Pizarra Study. Moreover, in the pooled population, we found a stronger association with waist circumference. Even, we found association with BMI. Furthermore, rs659366 polymorphism was associated with the risk of abdominal obesity (P = 0·04: OR = 1·3; CI = 1·01–1·67).

Conclusions  Polymorphisms of the UCP2 gene (rs660339 and rs659366) were associated with central obesity. This study shows association between the UCP2 gene and the susceptibility to obesity and body fat distribution in a south European population.
Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance
Authors: Poelzl Gerhard , Ess Michael , Mussner‐Seeber Christine , Pachinger Otmar , Frick Matthias , Ulmer Hanno
Published: June 2011

Eur J Clin Invest 2011

Background  Although abnormal liver morphology and function have long been recognized, characterization and importance of liver dysfunction in heart failure are poorly defined. This study sought to investigate the relevance of circulating liver function tests (LFTs) in an unselected chronic heart failure (CHF) cohort.

Materials and methods  A total of 1032 consecutive ambulatory patients with CHF were enrolled from 2000 to 2008. Clinical and laboratory variables including LFTs were collected at study entry. Follow‐up (median 36 months) was available in 1002 (97·1%) patients. The endpoint was defined as death from any cause or heart transplantation. Hazard ratios (HR) for transplant‐free survival were estimated per log unit using Cox proportional hazard regression models for sex‐stratified data.

Results  Sex‐specific prevalence of cholestatic enzyme elevation was 19·2% as opposed to elevated transaminases in 8·3%. Cholestatic enzymes, but not transaminases, were significantly associated with severity of heart failure syndrome and backward failure. The endpoint was recorded in 339 patients (33·8%). T‐Bil, γ‐glutamyltransferase (GGT) and alkaline phosphatase (ALP) were associated with adverse outcome in bivariate models. Of these, GGT [HR 1·22 (1·06, 1·41); P = 0·006] and ALP [HR 1·52 (1·09, 2·12); P = 0·014] were independently associated with the endpoint after adjustment for a wide array of clinical and laboratory predictors.

Conclusions  Liver dysfunction is frequent in CHF and characterized by a predominantly cholestatic enzyme profile that is associated with disease severity and prognosis. Thus, we propose a cardio‐hepatic syndrome in CHF. Future studies are needed to clarify the exact mechanisms of organ interaction.
Silicon concentration and leaf longevity: is silicon a player in the leaf dry mass spectrum?
Authors: Cooke Julia , Leishman Michelle R.
Published: June 2011

1. Multiple functions of plant silicon are known from agricultural species where silicon fertilizer alleviates biotic and abiotic stress impacts. In contrast, the function of plant silicon in natural ecosystems is often overlooked and is relatively poorly understood.

2. We investigated a potential integration of silicon with the leaf dry mass economics framework. We examined the relationship between leaf longevity, a trait considered to optimize leaf carbon use, and leaf silicon concentration across plant functional types and phylogenetic groups, testing the hypothesis that short‐lived leaves have higher silicon content to maximize carbon allocation to growth. We considered leaf longevity a continuous trait (months, n = 155 species) and a binary trait (annual vs. perennial, n = 602 species).

3. A significant negative correlation was found across all species between leaf longevity (months) and relative silicon concentration, indicating that across functional types and plant families, leaves with shorter life spans contain higher concentrations of silicon. A similar significant relationship was also found within deciduous angiosperm leaves. Silicon concentration was significantly higher in annual vs. perennial species across most plant functional types. Within order and family, no significant difference in silicon concentration was found between annual and perennial leaves except in the Poales and the Poaceae, where annual leaves had higher silicon concentration. Relative leaf/shoot silicon concentration varied much more than leaf longevity across the phylogeny, and there was a stronger phylogenetic signal from silicon concentration than from leaf longevity. Evolutionary divergence analysis showed that divergences between relative silicon concentration and leaf life span (months) were not significantly correlated; however, using a larger data set, leaf life span (as an annual/perennial binary trait) and relative silicon concentration were significantly correlated, implying that across a larger data set, shifts to higher relative leaf/shoot silicon concentration are consistently associated with shifts to annual foliage.

4. We suggest that in shorter‐lived leaves, silicon could be a metabolically cheaper alternative to carbon, allowing a more favourable leaf carbon balance over short periods. Silicon could be a less versatile, but more disposable resource, with the potential to function in structural, stress alleviation and defensive roles by substituting for carbon that could be allocated to further growth and reproduction.
Effects of silver diamine fluoride on dentine carious lesions induced by Streptococcus mutans and Actinomyces naeslundii biofilms
Authors: CHU CHUN HUNG , MEI LEI , SENEVIRATNE CHAMINDA JAYAMPATH , LO EDWARD CHIN MAN
Published: June 2011

International Journal of Paediatric Dentistry 2011; 22: 2–10

Background.  Silver diamine fluoride (SDF) has been shown to be a successful treatment for arresting caries. However, the mechanism of SDF is to be elucidated.

Aim.  To characterize the effects of SDF on dentine carious induced by Streptococcus mutans and Actinomyces naeslundii.

Design.  Thirty‐two artificially demineralized human dentine blocks were inoculated: 16 with S. mutans and 16 with A. naeslundii. Either SDF or water was applied to eight blocks in each group. Biofilm morphology, microbial kinetics and viability were evaluated by scanning electron microscopy, colony forming units, and confocal microscopy. The crosssection of the dentine carious lesions were assessed by microhardness testing, scanning electron microscopy with energy‐dispersive x‐ray spectroscopy and Fourier transform infrared spectroscopy.

Results.  Biofilm counts were reduced in SDF group than control (P < 0.01). Surfaces of carious lesions were harder after SDF application than after water application (P < 0.05), in S. mutans group, Ca and P weight percentage after SDF application than after water application (P < 0.05). Lesions showed a significantly reduced level of matrix to phosphate after SDF treatment (P < 0.05).

Conclusion.  Present study showed that SDF posses an anti‐microbial activity against cariogenic biofilm of S. mutans or A. naeslundii formed on dentine surfaces. SDF slowed down demineralization of dentine. This dual activity could be the reason behind clinical success of SDF.