Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children.

BACKGROUND: Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed. AIM: To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children. METHODS: Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes. RESULTS: Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children. CONCLUSION: Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

Experimental Analysis of Energy Transfers between a Quantum Emitter and Light Fields.

Energy can be transferred between two quantum systems in two forms: unitary energy-that can be used to drive another system-and correlation energy-that reflects past correlations. We propose and implement experimental protocols to access these energy transfers in interactions between a quantum emitter and light fields. Upon spontaneous emission, we measure the unitary energy transfer from the emitter to the light field and show that it never exceeds half the total energy transfer and is reduced when introducing decoherence. We then study the interference of the emitted field and a coherent laser field at a beam splitter and show that the nature of the energy transfer quantitatively depends on the quantum purity of the emitted field.

Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVES: The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). DESIGN: Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. SETTING: Four rehabilitation centres in the Netherlands. SUBJECTS: A total of 122 patients participated in the trial. MAIN OUTCOME MEASURES: Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. RESULTS: A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. CONCLUSION: This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial.

Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation.

Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPγS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes. h-neutrophil chemotaxis, degranulation and ROS production were established using CXCL8 or CXCL1 to evaluate dual CXCR1/2- or selective CXCR2-dependent activities. LPS-induced lung inflammation in gp was selected to assess in vivo potency. Dual CXCR1/2 antagonists blocked both CXCL8 and CXCL1-induced h-neutrophil functions and [(35)S]GTPγS binding. In contrary, selective CXCR2 antagonists displayed significantly reduced potency in CXCL8 -mediated h-neutrophil responses despite being active in CXCR2 assays. Upon LPS challenge in gp, administration of SCH527123 inhibited the increase of neutrophils in BALF, modestly reduced blood neutrophils and induced minor neutrophil accumulation in bone marrow. Differentiation of CXCR1/2 vs. CXCR2 antagonists could not be extended to in vivo due to differences in CXCR1 receptor homology between h and gp. Dual CXCR1/2 therapy may represent a promising anti-inflammatory treatment for respiratory diseases reducing more effectively neutrophil migration and activation in the lung than a CXCR2 selective treatment. However, the in vivo confirmation of this claim is still missing due to species differences in CXCR1.

Determination of lactones in wines by headspace solid-phase microextraction and gas chromatography coupled with mass spectrometry.

Application of headspace solid-phase microextraction (HS-SPME) coupled with high-resolution gas chromatographic (HRGC) analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few µg/L for the rest of the compounds. The optimized method has been applied to several wine samples.

Hospital-based cluster randomised controlled trial to assess effects of a multi-faceted programme on influenza vaccine coverage among hospital healthcare workers and nosocomial influenza in the Netherlands, 2009 to 2011.

Nosocomial influenza is a large burden in hospitals. Despite recommendations from the World Health Organization to vaccinate healthcare workers against influenza, vaccine uptake remains low in most European countries. We performed a pragmatic cluster randomised controlled trial in order to assess the effects of implementing a multi-faceted influenza immunisation programme on vaccine coverage in hospital healthcare workers (HCWs) and on in-patient morbidity. We included hospital HCWs of three intervention and three control University Medical Centers (UMCs), and 3,367 patients. An implementation programme was offered to the intervention UMCs to assess the effects on both vaccine uptake among hospital staff and patient morbidity. In 2009/10, the coverage of seasonal, the first and second dose of pandemic influenza vaccine as well as seasonal vaccine in 2010/11 was higher in intervention UMCs than control UMCs (all p<0.05). At the internal medicine departments of the intervention group with higher vaccine coverage compared to the control group, nosocomial influenza and/or pneumonia was recorded in 3.9% and 9.7% of patients of intervention and control UMCs, respectively (p=0.015). Though potential bias could not be completely ruled out, an increase in vaccine coverage was associated with decreased patient in-hospital morbidity from influenza and/or pneumonia.

[Female sexuality after surgical treatment of symptomatic deep pelvic endometriosis]. / Sexualité féminine après chirurgie pour endométriose pelvienne profonde.

OBJECTIVES: The aim of this study is to assess the impact on sexuality of the surgical treatment in patients with symptomatic deep pelvic endometriosis. PATIENTS AND METHODS: The design is a single-center cohort prospective study including all patients with symptomatic pelvic endometriosis and regular sexual activity who underwent surgery between October 2009 and September 2010. Sexual function was evaluated by the "Brief Index of Sexual Functioning for Women" (BISF-W) questionnaire translated and validated in French, including a global evaluation by the Composite Score (CS). Pain symptoms related to endometriosis were evaluated by the Visual Analog Scale (VAS) and the simple Verbal Rating Scale (VRS). Questionnaires were answered before surgery. A standardized mid and long-term postoperative follow-up was performed to compare sexuality and pain symptoms. RESULTS: Twenty women were included in the study. Mean follow-up was 23.3 months. When compared to a French reference population, global preoperative sexual function was significatively deteriorated (CS=14.3±10.8 vs 32.2±12.6; P<0.001), especially for arousal, frequency of sexual activity, pleasure and orgasm. Significant improvements in sex life were observed after surgery at the long-term follow-up (CS=33.0±11.7 vs 14.3±10.8; P=0.02). and sexual function was similar to the reference population (CS=33.0±11.7 vs 32.2±12.6; P=0.806). At the mid-follow-up, a significant improvement in the intensity of dysmenorrhoea, non-cyclic pelvic pain, dyspareunia and bowel symptoms were observed on the VAS. At the long-term follow-up, dysmenorrhoea and dyspareunia were significatively ameliorated. Pelvic pain recurrence related to endometriosis was 13.3%. DISCUSSION AND CONCLUSION: Surgical management of deep pelvic endometriosis in symptomatic patients improves sexual life at the long term follow-up. Deep dyspareunia pain decreases significantly, although other conditions are involved in the improvement of sexual function.

Profiling of dihydroorotate dehydrogenase, p38 and JAK inhibitors in the rat adjuvant-induced arthritis model: a translational study.

BACKGROUND AND PURPOSE: Translational animal models are essential in the prediction of the efficacy and side effects of new chemical entities. We have carried out a thorough study of three distinct disease-modifying antirheumatic drugs (DMARDs) in an adjuvant-induced arthritis (AIA) model in the rat and critically appraised the results in the context of the reported clinical experience in rheumatoid arthritis (RA) patients. EXPERIMENTAL APPROACH: Teriflunomide - a dihydroorotate dehydrogenase (DHODH) inhibitor; AL8697 - a selective p38 MAPK inhibitor; and tofacitinib - a Janus kinase (JAK) inhibitor; were selected as representatives of their class and dose-response studies carried out using a therapeutic 10-day administration scheme in arthritic rats. Paw swelling and body weight were periodically monitored, and joint radiology and histology, lymph organ weight and haematological and biochemical parameters evaluated at study completion. KEY RESULTS: All three drugs demonstrated beneficial effects on paw swelling, bone lesions and splenomegalia, with p38 inhibition providing the best anti-inflammatory effect and JAK inhibition the best DMARD effect. Leukopenia, body weight loss and gastrointestinal toxicity were dose-dependently observed with teriflunomide treatment. p38 MAPK inhibition induced leukocytosis and increased total plasma cholesterol. JAK inhibition, normalized platelet, reticulocyte and neutrophil counts, and alanine aminotransferase (ALT) levels while inducing lymphopenia and cholesterolemia. CONCLUSIONS AND IMPLICATIONS: This multiparametric approach can reveal specific drug properties and provide translational information. Whereas the complex profile for p38 inhibition in AIA is not observed in human RA, immunosuppressants such as DHODH and JAK inhibitors show DMARD properties and side effects seen in both AIA and RA.

Determination of factors required to increase uptake of influenza vaccination among hospital-based healthcare workers.

A questionnaire study was performed in all eight University Medical Centers in The Netherlands to determine the predictors of influenza vaccination compliance in hospital-based healthcare workers (HCWs). Demographical, behavioural and organisational determinants were assessed based on behavioural and implementation models. Multivariable regression analysis was applied to assess the independent predictors for influenza vaccine uptake. Age >40 years, the presence of a chronic illness, awareness of personal risk and awareness of risk of infecting patients, trust in the effectiveness of the vaccine to reduce the risk of infecting patients, the HCWs' duty to do no harm and their duty to ensure continuity of care, finding vaccination useful despite the constant flow of visitors and having knowledge of the Health Council's advice, social influence and convenient time for vaccination were all independently associated with vaccine uptake. The accuracy of the prediction model was very high (area under the receiver operating curve: 0.95). Intervention programmes to increase influenza vaccine uptake among HCWs should target the relevant determinants identified in this study.

[Placenta percreta at first trimester of pregnancy. Diagnostic and decision-making difficulties: about a case and a review of the literature]. / Placenta percreta en fin de premier trimestre de grossesse. Difficultés diagnostique et décisionnelle: à propos d'un cas et revue de la littérature.

We report the case of a 28-year-old patient, G9P4. Her last pregnancy was marked by a failure of a medical termination at 4 gestational weeks. She consulted as a matter of emergency for acute abdominal pain with moderated hemoperitoneum at 13 weeks of gestation. A laparotomy was performed and allowed to diagnose a placenta percreta (PPer). The treatment consisted in a hemostasis hysterectomy. The PPer is a rare pathology. The diagnosis is difficult to do, especially during the first and second trimester of the pregnancy. The focus of this article is to evaluate medical imaging and conservative treatments or radical treatment, according to the severity of the symptoms and her obstetrical outcome. This unusual etiology of hemoperitoneum at 13 weeks of gestation must to be known in front of the increase of the caesarians rate.

[Abdominal migration of a levonorgestrel-releasing intrauterine device. Case report and review of the literature]. / Efficacité d'un stérilet au levonorgestrel migré en intra-abdominal. A propos d'un cas et revue de la littérature.

We report the case of a 27-year-old woman in amenorrhea after the installation of a levonorgestrel releasing intra-uterine device, 3 years previously. In front of pelvic continuing pains, paraclinic explorations diagnosed the DIU-LNG in intra-abdominal situation. An exploratory laparoscopy was realized and allowed its ablation. The authors discuss the systemic distribution of the levonorgestrel and the impact of the DIU-LNG in intra-abdominal situation by a review of the literature.

Maternal and neonatal characteristics of extremely low birth weight infants who die in the first day of life.

OBJECTIVE: To determine changes over time in the characteristics of early extremely low birth weight non-survivors (E-ELBW-NS), maternal characteristics and perinatal management, and the documentation of perinatal consultations. STUDY DESIGN: We conducted a chart review of infants <750 g who died within 24 h divided into two epochs: 1 January 1995 to 31 December 1999 and 1 January 2000 to 31 December 2005. Maternal and neonatal characteristics, delivery room resuscitation, post-resuscitation care, and documentation of resuscitation and perinatal counseling were examined. RESULT: A total of 138 infants met inclusion criteria. During Epoch 2, there was an increase in black, small for gestational age infants and prior maternal preterm delivery, and decreased incidences of tocolysis and chorioamnionitis. Also, a trend toward more hemolysis elevated liver enzymes and low platelet syndrome and decreased prenatal care existed. Perinatal consultations increased in both number and quality with time. CONCLUSION: There has been a shift in racial distribution toward more black infants in the second epoch perhaps reflecting disparities in care. Otherwise, demographics and management of E-ELBW-NS have changed minimally. There has been a significant improvement in the documentation of perinatal consultations.

Chronic anorexia nervosa: enteral nutrition via percutaneous endoscopic gastrostomy and liaison psychiatry.

Anorexia nervosa is a complex mental disorder characterized by altered eating behaviour often resulting in life-threatening weight loss (<85% of expected body weight) associated with amenorrhea and a disturbance of body image. Although classified as mental health disorders, they may lead to serious medical consequences and have the highest rate of premature death of any mental health diagnosis. We report our experience with the use of enteral feeding via percutaneous endoscopic gastrostomy in a 39-year-old woman with chronic restricter anorexia nervosa treated in liaison psychiatry and psychotherapy. On admission to psychiatry unit, the patient presented seriously deteriorated general condition and a body mass index (BMI) of 10 (BMI = weight kg/height m(2)). She refused oral feeding, but eventually accepted nasogastric feeding. In preparation for her continuing long-term (>1 month) enteral feeding at home, a percutaneous endoscopic gastrostomy was performed and a home nutrition support regimen that met her energy-protein intake requirements was prescribed. During the follow-up period, an overall improvement in nutritional status, general condition, mood and cognitive functioning was observed. Patient compliance with refeeding is notoriously problematic; however, enteral feeding interventions may be feasible in the long-term treatment of selected anorexia nervosa patients when closely followed-up by a multidisciplinary medical team.

Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants.

OBJECTIVE: To examine whether hypercapnia in very low birth weight (VLBW) infants during the first 3 days of life is associated with severe intraventricular hemorrhage (IVH). STUDY DESIGN: Retrospective cohort study of inborn VLBW infants between January 1999 and May 2004 with arterial access during the first 3 days of life. A multiple logistic regression analysis was used where IVH was dichotomized ((grades 0/1/2) = non-severe; (grades 3/4) = severe). Measures of hypercapnia were entered into the model to ascertain their association with severe IVH. RESULTS: In total, 574 VLBW infants met entry criteria. Worst IVH grade was 0 in 400; 1: 54; 2: 42; 3: 47; and 4: 31 infants. The logistic regression model consisted of the following predictors of severe IVH: gestational age, gender, 1 min Apgar score (dichotomized into two groups: >3 vs < or =3), multifetal gestation, vasopressor use, and maximum PaCO(2). CONCLUSION: In addition to traditional risk factors, it appears maximum PaCO(2) is a dose-dependent predictor of severe IVH during the permissive hypercapnia era.

A computerized database of 'normal' auditory brainstem responses.

A computerized database of auditory brainstem responses (ABRs) from 'normal-hearing' volunteers is described. The database contains 'raw' responses recorded from 81 individuals; subjects varied in age from 20 to 56 years. The database is currently being used in a study to aid in the interpretation of ABRs for diagnostic purposes. Copies of the database are available over the world-wide web (http:¿¿www.engg.le.ac.uk¿abrdata).

[Solar urticaria: pre-PUVA UVA desensitization]. / Urticaire solaire : désensibilisation UVA avant PUVAthérapie.

BACKGROUND: Solar urticaria is an uncommon disorder sometimes difficult to treat. It is characterized by the occurrence of typical whealing reactions on exposed skin a few minutes after sun exposure. The reactions resolve 1 to 5 hours after sun exposure ceases. We report a case evolving over several years, unresponsive to antihistamines and successfully treated by PUVAtherapy performed after UVA desensitization. CASE REPORT: For 3 years, a 22-year-old man developed erythema and itchy wheals at each solar exposure. The lesions appeared on all exposed areas including those usually exposed (face and hand) even in winter. An antihistamine regimen given for several weeks (cetirizine, loratadine) was ineffective. One trial of PUVA therapy led to an urticarial reaction of the entire body. Phototesting showed the minimal whealing dose for UVA was 0.4 J/cm(2). Phototherapy was therefore started by segmentary UVA irradiation at an initial dose of 0.1 J/cm(2). Exposure was then progressively increased allowing initiation of the PUVAtherapy on the 9(th) day with a dose of 0.5 J/cm(2) without whealing reaction. Slow increment PUVA therapy was able to induce good tolerance to sun exposure. DISCUSSION: Solar urticaria may sometimes have a deleterious effect on normal daily life. Severe cases are characterized by a whealing reaction after minimal sun exposure, even on regularly exposed skin. Antihistamines can provide some symptom relief in many patients, but high doses are required. If antihistamines are ineffective, PUVA therapy is indicated. Pre-PUVA UVA desensitization is often necessary. However, exposure to UVA alone has to be repeated every 24 to 48 hours to maintain the refractory state. The advantage of PUVA therapy is a more long lasting protection allowing weekly maintenance sessions.