Approaches to discontinuing efalizumab: an open-label study of therapies for managing inflammatory recurrence

BACKGROUND: Efalizumab is a humanised recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of efalizumab. METHODS: An open-label, multicentre, investigational study was performed in 41 patients with moderate-to-severe plaque psoriasis who had recently completed clinical studies with efalizumab and had developed signs of inflammatory recurrence following abrupt cessation of treatment. Patients were assigned by the attending physicians to receive one of five standardised alternative systemic psoriasis treatment regimens for 12 weeks. Efficacy of the different therapy options was assessed using the physician's global assessment (PGA) of change over time. RESULTS: More favourable PGA responses were observed in patients changing to cyclosporin (PGA of 'good', 'excellent' or 'cleared': 7/10 patients, 70.0%) or methotrexate (9/20, 45.0%), compared with those receiving systemic corticosteroids (2/8, 25.0%), retinoids (0/1, 0.0%) or combined corticosteroids plus methotrexate (0/2, 0.0%). While the majority (77.8%) of patients showed inflammatory morphology at baseline, following 12 weeks of the alternative therapies the overall prevalence of inflammatory disease was decreased to 19.2%. CONCLUSION: Inflammatory recurrence after discontinuation of efalizumab therapy is a manageable event, with a number of therapies and approaches available to physicians, including short courses of cyclosporin or methotrexate

Automatic colorimetric calibration of human wounds

Contains fulltext : 88431.pdf (publisher's version ) (Open Access)BACKGROUND: Recently, digital photography in medicine is considered an acceptable tool in many clinical domains, e.g. wound care. Although ever higher resolutions are available, reproducibility is still poor and visual comparison of images remains difficult. This is even more the case for measurements performed on such images (colour, area, etc.). This problem is often neglected and images are freely compared and exchanged without further thought. METHODS: The first experiment checked whether camera settings or lighting conditions could negatively affect the quality of colorimetric calibration. Digital images plus a calibration chart were exposed to a variety of conditions. Precision and accuracy of colours after calibration were quantitatively assessed with a probability distribution for perceptual colour differences (dE_ab). The second experiment was designed to assess the impact of the automatic calibration procedure (i.e. chart detection) on real-world measurements. 40 Different images of real wounds were acquired and a region of interest was selected in each image. 3 Rotated versions of each image were automatically calibrated and colour differences were calculated. RESULTS: 1st Experiment: Colour differences between the measurements and real spectrophotometric measurements reveal median dE_ab values respectively 6.40 for the proper patches of calibrated normal images and 17.75 for uncalibrated images demonstrating an important improvement in accuracy after calibration. The reproducibility, visualized by the probability distribution of the dE_ab errors between 2 measurements of the patches of the images has a median of 3.43 dE* for all calibrated images, 23.26 dE_ab for all uncalibrated images. If we restrict ourselves to the proper patches of normal calibrated images the median is only 2.58 dE_ab! Wilcoxon sum-rank testing (p < 0.05) between uncalibrated normal images and calibrated normal images with proper squares were equal to 0 demonstrating a highly significant improvement of reproducibility. In the second experiment, the reproducibility of the chart detection during automatic calibration is presented using a probability distribution of dE_ab errors between 2 measurements of the same ROI. CONCLUSION: The investigators proposed an automatic colour calibration algorithm that ensures reproducible colour content of digital images. Evidence was provided that images taken with commercially available digital cameras can be calibrated independently of any camera settings and illumination features

Modulation of Interleukin-1 Transcriptional Response by the Interaction between VRK2 and the JIP1 Scaffold Protein

Background. Cellular biological responses to specific stimulation are determined by a balance among signaling pathways. Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways. Principal findings. We report that in vivo, the activity of JIP1-JNK complexes is downregulated by VRK2 in response to interleukin-1β. Also the reduction of endogenous VRK2 with shRNA increases the transcriptional response to IL-1β. The JIP1 scaffold protein assembles three consecutive members of a given MAPK pathway forming signaling complexes and their signal can be modulated by interactions with regulatory proteins that remain to be identified. Knocking-down JIP1 with siRNA resulted in elimination of the AP1 transcriptional response to IL-1β. VRK2, a member of novel Ser-Thr kinase family, is able to stably interact with JIP1, TAK1 and MKK7, but not JNK, and can be isolated forming oligomeric complexes with different proportions of TAK1, MKK7β1 and JNK. JIP1 assembles all these proteins in an oligomeric signalosome. VRK2 binding to the JIP1 signalosome prevents the association of JNK and results in a reduction in its phosphorylation and downregulation of AP1-dependent transcription. Conclusions/Significance. This work suggests that the intracellular level of VRK2 protein can modulate the flow through a signaling pathway and alter the response from a receptor that can be distributed by more than one pathway, and thus contribute to the cellular specificity of the response by forming alternative signaling complexes. Furthermore, the effect might be more general and affect other signaling routes assembled on the JIP1 scaffold protein for which a model is proposed.S.B., M. S-G, and C.R.S. have predoctoral fellowships from Ministerio de Educación y Ciencia, CSIC (Spain) and Fundação para a Ciência e a Tecnologia (Portugal) respectively. This work was funded by grants from Ministerio de Educación y Ciencia (SAF2004-02900, SAF2007-60242 and Consolider CSD-2007-0017), Fundación de Investigación Médica MM and Federación de Cajas de Ahorro de Castilla y León to P.A.L.Peer reviewe

Effect on skin hydration of using baby wipes to clean the napkin area of newborn babies: assessor-blinded randomised controlled equivalence trial

Background Some national guidelines recommend the use of water alone for napkin cleansing. Yet, there is a readiness, amongst many parents, to use baby wipes. Evidence from randomised controlled trials, of the effect of baby wipes on newborn skin integrity is lacking. We conducted a study to examine the hypothesis that the use of a specifically formulated cleansing wipe on the napkin area of newborn infants (<1 month) has an equivalent effect on skin hydration when compared with using cotton wool and water (usual care). Methods A prospective, assessor-blinded, randomised controlled equivalence trial was conducted during 2010. Healthy, term babies (n = 280), recruited within 48 hours of birth, were randomly assigned to have their napkin area cleansed with an alcohol-free baby wipe (140 babies) or cotton wool and water (140 babies). Primary outcome was change in hydration from within 48 hours of birth to 4 weeks post-birth. Secondary outcomes comprised changes in trans-epidermal water loss, skin surface pH and erythema, presence of microbial skin contaminants/irritants at 4 weeks and napkin dermatitis reported by midwife at 4 weeks and mother during the 4 weeks. Results Complete hydration data were obtained for 254 (90.7 %) babies. Wipes were shown to be equivalent to water and cotton wool in terms of skin hydration (intention-to-treat analysis: wipes 65.4 (SD 12.4) vs. water 63.5 (14.2), p = 0.47, 95 % CI -2.5 to 4.2; per protocol analysis: wipes 64.6 (12.4) vs. water 63.6 (14.3), p = 0.53, 95 % CI -2.4 to 4.2). No significant differences were found in the secondary outcomes, except for maternal-reported napkin dermatitis, which was higher in the water group (p = 0.025 for complete responses). Conclusions Baby wipes had an equivalent effect on skin hydration when compared with cotton wool and water. We found no evidence of any adverse effects of using these wipes. These findings offer reassurance to parents who choose to use baby wipes and to health professionals who support their use. Trial registration Current Controlled Trials ISRCTN8620701

Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes

<p>Abstract</p> <p>Background</p> <p>Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.</p> <p>Case Presentation</p> <p>The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes the <it>SALL1 </it>gene, which causes Townes-Brocks syndrome.</p> <p>Conclusions</p> <p>Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includes <it>SALL1</it>, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by the <it>SALL1 </it>deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.</p

Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash.sup.TM methylated quantification colorimetric assay. These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population

The quality of life of patients with genital warts: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Genital warts, which are caused by infection with human papillomavirus (HPV), are one of the most common sexually transmitted diseases in Europe. Although genital warts are commonly perceived as a non-serious condition, treatment is often long, of varying effectiveness and the recurrence rate is high. Very few studies have been performed on the personal consequences of genital warts. The aim of this qualitative study, set in Denmark, was to examine the ways in which genital warts may affect patients' quality of life.</p> <p>Methods</p> <p>To obtain an in-depth understanding of patients' perceptions of genital warts, we used qualitative focus-group interviews with five men and five women aged between 18 and 30 years who had genital warts. The interview guide was based on a literature review that identified important issues and questions. The data were analysed using a medical anthropological approach.</p> <p>Results</p> <p>Patients' experiences were related to cultural conceptions of venereal diseases and the respective identities and sexuality of the sexes. The disease had negative psychological and social effects both for men and for women and it affected their sex and love lives, in particular. The psychological burden of the disease was increased by the uncertain timeline and the varying effectiveness of treatment. We identified a need for more patient information about the disease and its psycho-sexual aspects.</p> <p>Conclusions</p> <p>The men and women participating in this study considered their quality of life to be significantly lowered because of genital warts. The experiences described by the participants give insights that may be valuable in treatment and counselling.</p> <p>The quadrivalent HPV vaccine that has now been added to the childhood vaccination programme for girls in Denmark for the prevention of cervical cancer can also prevent 90% of cases of genital warts. Our results suggest that HPV vaccination could considerably reduce the largely unacknowledged psychological and social burden associated with genital warts, in men as well as women.</p