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Summary Background Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have been scarcely reported. Objectives To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention-to-treat analysis. Results We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n = 24), adalimumab (n = 7), etanercept (n = 6), ustekinumab (n = 3) or efalizumab (n = 2). A 75% improvement of BSA or Psoriais Area and Severity Index 12–14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events, consisting of bacterial infection in seven of them, were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was administered for up to 48 weeks in 34% of flares. Conclusions Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side-effects is frequently observed on a longer term, with only one-third of patients still receiving the same drug after 1 year. The most significant safety concern consists of severe infections.

To study the effect of concurrent psychiatric disorders on health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA).Consecutive Chinese patients who fulfilled the American College of Rheumatology (ACR) criteria for RA were recruited and interviewed by a psychiatrist for psychiatric disorders using the Chinese Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders, Patient version (CB-SCID-I/P). HRQOL was assessed by the validated Chinese version of the 36-item Short Form Health Survey (SF-36). Sociodemographic and clinical data were also collected. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F).Two hundred patients with RA were studied (79% women, mean age 51.4 ± 10.5 years; median RA duration 4.0 years). Forty-seven (23.5%) patients were diagnosed with a psychiatric disorder: depressive disorders in 29 patients and anxiety disorders in 26 patients. Patients with either condition had significantly higher fatigue scores (26 ± 8.8 vs. 16 ± 6.9, p0.001) and were more likely to be unemployed (p = 0.02) and dependent on government subsidy for living (p0.001) than those without. The scores of the eight domains and the physical and mental components of the SF-36 were significantly lower in RA patients with psychiatric disorders (p0.001 in all). In a linear regression model, the presence of either depressive or anxiety disorders (β = -0.23, p0.001), older age (β = -0.16, p = 0.006), self-perceived pain (β = -0.25, p0.001) and fatigue (β = -0.42, p0.001) were independently and inversely associated with the total SF-36 score after adjustment for disease activity and other sociodemographic variables.Concomitant depressive or anxiety disorders in RA patients are associated with significantly poorer HRQOL. Early identification and treatment of psychiatric disorders in RA patients are warranted.

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of DU

We recorded side effects and other complications of 813 plasma exchanges used in early treatment of polyarteritis nodosa and Churg-Strauss angiitis in a prospective study of 72 patients (22-75 years old). All the patients were also treated with a corticosteroid (1 mg/kg/day), and half were included in a randomized trial of cyclophosphamide (2 mg/kg/day during 1 year). Centrifugation was used in 678 plasma exchange sessions (83.4%) and filtration in 128 (15.7%) (no data were available about the technique used in seven cases). The replacement fluid in 745 sessions was 4% albumin and in 115 was fresh-frozen plasma; eight patients received both (47 sessions). Two hundred and fifty-one complications were reported in 60 patients during 206 (25.3%) of the 813 completed exchanges; 47 sessions (5.8%) were temporarily stopped as a result of complications. The most common problems were technical difficulties (in 90 sessions), moderate or severe hypotension (in 52), and allergy to the replacement fluid (in 51). Hepatitis B antigen appeared in one patient. In four patients, plasma exchange was stopped permanently because of the severe side effects. No patient died during a session. Twelve of the 72 patients died during the study, six in each of the two groups. In the group treated by a combination of corticosteroid and plasma exchange, deaths were related to the deleterious effects of the disease itself and occurred after 12.8 +/- 11.1 months (1-26 months). In the group treated by the same combination plus cyclophosphamide, four of the six deaths were due to severe infections, which were related to leukopenia in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A series of novel water-soluble, bioreducible poly(amido amine)s containing disulfide linkages in their amino units (SS-PAAs) was synthesized by Michael addition polymerization of N,N′-dimethylcystamine (DMC) with various bisacrylamides. The synthetic route allows large structural variation in the bisacrylamide segments and is complementary to the earlier developed route to SS-PAAs in which the disulfide bond is incorporated in cystamine bisacrylamide units. The physicochemical and biomedical properties of the novel DMC-based polymers were evaluated for their application as non-viral gene delivery vectors and compared with analogs lacking the disulfide moieties. DMC-based SS-PAAs show high buffer capacities in the pH range pH 5.1–7.4, a property that may favorably contribute to the endosomal escape of the polyplexes. The polymers are capable to condense DNA into nanoscaled (< 250 nm) and positively charged (>+ 20 mV) polyplexes which are relatively stable in medium mimicking physiological conditions but rapidly disintegrate in the presence of 2.5 mM DTT, mimicking the intracellular reductive environment. Polyplexes from DMC-based SS-PAAs are capable to transfect COS-7 cells in vitro with transfection efficiencies up to 4 times higher than those of pDMAEMA and PEI, with no or only very low cytotoxicity at the polymer/DNA ratios where the highest transfection is observed. The results show that DMC-based SS-PAAs have very promising properties for the development of potent and non-toxic polymeric gene carriers.

Purpose The risk of infection can be reduced in hemodialysis (HD) patients with central venous catheters (CVCs) by using prophylactic intranasal mupirocin or polysporin at the exit site. However, there are concerns about the potential emergence of resistant microorganisms. The purpose of our study was to determine if the use of polysporin double in the treatment of exit site infections was associated with the emergence of yeast positive exit site cultures. Methods In this case control study, we evaluated the risk of developing yeast positive exit site cultures after introducing a polysporin medical directive for the treatment of presumed exit site infections in our HD units. All HD patients using a CVC for blood access at the Ottawa Hospital were eligible for study. Demographic variables, use of polysporin, antibiotics and immunosuppressive medications were compared between those patients with yeast positive exit site cultures and controls. Results There was no differences in age, gender or diabetic status between the cases and controls. However, the use of polysporin, antibiotics and immunocompromised status were associated with an increased risk of yeast positive exit site cultures. The relative importance of each of these factors could not be determined using this study design and requires future prospective study. Conclusions The emergence of yeast positive exit site cultures after the introduction of a new medical directive at a tertiary care hospital highlights the difference between medications used for prophylaxis and those used for treatment of CVC infections in high risk dialysis patients.

Objective: To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). Methods: In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results: Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion: This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. © 2016, American College of Rheumatology

Brushed polymers composed of a backbone of poly(hydroxyethyl methacrylate) (pHEMA) onto which poly(2-(dimethylamino)ethyl methacrylate)s (pDMAEMAs) was grafted via a hydrolyzable linker were synthesized and evaluated as nonviral gene delivery vectors. Both pDMAEMA and pHEMA polymers with controlled molecular weights and narrow distributions were synthesized by controlled atom transfer radical polymerization (ATRP). The azide initiator was used to ensure complete and monoazide functionalization of the pDMAEMA polymer chains. Click reaction between pHEMA with alkyne side groups and the azide end group in the pDMAEMA resulted in a high-molecular-weight polymer composed of low-molecular-weight constituents via an easily degradable carbonate ester linker. The length of the pDMAEMA grafts as well as the number of grafts of the brushed pHEMA-pDMAEMA can be easily varied. At physiological conditions (pH 7.4 and 37 degrees C), the brushed polymer degraded by hydrolysis of the carbonate ester with a half-life of 96 h. The molecular weights of the formed degradation products was very close to that of the starting pDMAEMA, which is likely below the renal excretion limit (30 kDa). It was shown that the degradable brushed pHEMA-pDMAEMAs were able to condense plasmid DNA into positively charged nanosized particles. The resulting polyplexes were able to transfect cells efficiently in the presence of the endosomal membrane disrupting INF-7 peptide, and all these degradable polymers showed lower cellular toxicity compared to a high-molecular-weight pDMAEMA reference. On the other hand, the low-molecular-weight pDMAEMA used for the grafting to pHEMA was neither able to condense the structure of DNA nor able to transfect cells. This study demonstrates that grafting a low-molecular-weight cationic polymer via a hydrolyzable linker to a neutral hydrophilic polymer is an effective approach to modulate the transfection activity and toxicity profile of gene delivery polymers.

In contrast with bone metastasis, acrometastases are uncommon and are associated with advanced cancer. We report the cases of two patients with atypical lesions of the fingers in a context of cancer, in which biopsies confirmed a metastasis. Patients died rapidly before treatment was initiated. We discuss the characteristics of these atypical metastatic sites, associated with a generally poor prognosis.

OBJECTIVES: To determine the mechanism and epidemiology of paediatric finger injuries in Hong Kong during 2003-2005 and 2010-2012. DESIGN: Comparison of two case series. SETTING: University-affiliated teaching hospital, Hong Kong. PATIENTS: A retrospective study of two cohorts of children (age, 0 to 16 years) admitted to Prince of Wales Hospital with finger injuries during two 3-year periods. Comparisons were made between the two groups for age, involved finger(s), mechanism of injury, treatment, and outcome. Telephone interviews were conducted for parents of children who sustained a crushing injury of finger(s) by door. RESULTS: A total of 137 children (group A) were admitted from 1 January 2003 to 31 December 2005, and 109 children (group B) were admitted from 1 January 2010 to 31 December 2012. Overall, the mechanisms and epidemiology of paediatric finger injuries were similar between groups A and B. Most finger injuries occurred in children younger than 5 years (group A, 55%; group B, 75%) and in their home (group A, 67%; group B, 69%). The most common mechanism was crushing injury of finger by door (group A, 33%; group B, 41%) on the hinge side (group A, 63%; group B, 64%). The right hand was most commonly involved. The door was often closed by another child (group A, 37%; group B, 23%) and the injury often occurred in the presence of adults (group A, 60%; group B, 56%). Nailbed injury was the commonest type of injury (group A, 31%; group B, 49%). Fractures occurred in 24% and 49% in groups A and B, respectively. Traumatic finger amputation requiring replantation or revascularisation occurred in 12% and 10% in groups A and B, respectively. CONCLUSIONS: Crushing injury of finger by door is the most common mechanism of injury among younger children and accounts for a large number of hospital admissions. Serious injuries, such as amputations leading to considerable morbidity, can result. Crushing injury of finger by door occurs even in the presence of adults. There has been no significant decrease in the number of crushing injuries of finger by door in the 5 years between the two studies despite easily available and affordable preventive measures. It is the authors' view that measures aimed at promoting public awareness and education, and safety precautions are needed. Language: en

A series of novel bioreducible poly(amido amine)s containing multiple disulfide linkages (SS-PAAs) were synthesized and evaluated as nonviral gene vectors. These linear SS-PAAs could be easily obtained by Michael-type polyaddition of various primary amines to the disulfide-containing cystamine bisacrylamide. The SS-PAA polymers are relatively stable in medium mimicking physiological conditions (pH 7.4, 150 mM PBS, 37 degrees C), but are rapidly degraded in the presence of 2.5 mM DTT, mimicking the intracellular reductive environment (pH 7.4, [R-SH] = 5 mM, 37 degrees C). The polymers efficiently condense DNA into nanoscaled (200 nm) and positively charged (+20 mV) polyplexes that are stable under neutral conditions but are rapidly destabilized in a reductive environment, as was revealed by both dynamic light scatting measurement and agarose gel assays. Moreover, most of the poly(amido amine)s possess buffer capacities in the pH range pH 7.4-5.1 that are even higher than polyethylenimine (pEI), a property that may favorably contribute to the endosomal escape of the polyplexes. Polyplexes of four of the seven SS-PAAs studied were able to transfect COS-7 cells in vitro with transfection efficiencies significantly higher than those of branched pEI, being one of the most effective polymeric gene carriers reported to date. Importantly, also in the presence of serum, a high level of gene expression could be observed when the incubation time was elongated from 1 h to 4 h. XTT assays showed that SS-PAAs and their polyplexes possess essentially no or only very low cytotoxicity at concentrations where the highest transfection activity is observed. The results indicate that bioreducible poly(amido amine)s have excellent properties for the development of highly potent and nontoxic polymeric gene carriers.

Resume La maladie de Lhermitte-Duclos, appelee encore « gangliocytome dysplasique cerebelleux », est une entite rare, caracterisee par une lesion hamartomateuse en fosse posterieure. Le syndrome de Cowden, ou « syndrome des neoplasies-hamartomes », rare et sous-diagnostique, est une genodermatose autosomique dominante, avec haute incidence de tumeurs malignes. Plusieurs cas cliniques recents montrent que la maladie de Lhermitte-Duclos peut s’integrer dans le cadre d’un syndrome de Cowden. Les auteurs rapportent deux cas de maladie de Lhermite-Duclos avec syndrome de Cowden chez des patients adultes. Le premier cas est celui d’une femme de 40 ans, qui presentait une hypertension intracrânienne avec macrocephalie, une dysplasie fibrokystique de sein ainsi qu’un goitre thyroidien ; l’examen clinique montrait des lesions cutaneo-muqueuses ; sa mere, son pere et un oncle avaient des manifestations de syndrome de Cowden. Le second cas est celui d’un homme de 38 ans, qui avait un œdeme papillaire en relation avec une tumeur cerebelleuse ; il avait des antecedents entrant dans le cadre d’un syndrome de Cowden et son histoire familiale confirmait cette hypothese. Le premier patient etait opere pour sa maladie de Lhermitte-Duclos. Une attitude de surveillance etait envisagee pour le second, avec un recul clinique et radiologique tout a fait stables de plus de 7 ans. Nous pensons que la maladie de Lhermitte-Duclos et le syndrome de Cowden constituent un type de phacomatose. Une attitude expectative peut etre envisageable en raison du faible potentiel evolutif de croissance tumorale. Cependant, ces patients doivent etre examines avec attention en raison du risque de degenerescence tumorale maligne.

Novel ABA triblock copolymers consisting of low molecular weight linear polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B block were prepared and evaluated as polymeric transfectant. The cationic polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG-bis(tosylate) as a macroinitiator followed by acid hydrolysis afforded linear PEI-PEG-PEI triblock copolymers with controlled compositions. Two copolymers, PEI-PEG-PEI 2100-3400-2100 and 4000-3400-4000, were synthesized. Both copolymers were shown to interact with and condense plasmid DNA effectively to give polymer/DNA complexes (polyplexes) of small sizes (100 nm) and moderate zeta-potentials (approximately +10 mV) at polymer/plasmid weight ratiosor =1.5/1. These polyplexes were able to efficiently transfect COS-7 cells and primary bovine endothelial cells (BAECs) in vitro. For example, PEI-PEG-PEI 4000-3400-4000 based polyplexes showed a transfection efficiency comparable to polyplexes of branched PEI 25000. The transfection activity of polyplexes of PEI-PEG-PEI 4000-3400-4000 in BAECs using luciferase as a reporter gene was 3-fold higher than that for linear PEI 25000/DNA formulations. Importantly, the presence of serum in the transfection medium had no inhibitive effect on the transfection activity of the PEI-PEG-PEI polyplexes. These PEI-PEG-PEI triblock copolymers displayed also an improved safety profile in comparison with high molecular weight PEIs, since the cytotoxicity of the polyplex formulations was very low under conditions where high transgene expression was found. Therefore, linear PEI-PEG-PEI triblock copolymers are an attractive novel class of nonviral gene delivery systems.

Post-transplant cutaneous lymphomas are rare. Cutaneous T-cell lymphomas account for 30% of these lymphomas. The clinical appearance of the skin lesions is identical to cutaneous lymphomas observed in non-immunosuppressed patients, with infiltrated plaques, nodular and ulcerated tumors, but with an increased frequency of erythroderma. Standard histology and immunohistochemistry are also consistent with the features of mycosis fungoides and CD30+ cutaneous lymphomas observed in the general population. However, the pronostic differs from the usually favourable outcome of cutaneous T-cell lymphomas, as 8 out of the 13 patients of our series died, in less than 1 year for 6 of them. This unfavourable course appears to be the same as that observed for systemic T-cell lymphoma in transplant recipients. In contrast to post-transplant B-cell lymphomas (systemic and primary cutaneous), the link to a virus has not been demonstrated. The prognosis is also less favourable for post-transplant cutaneous T-cell lymphomas than for post-transplant cutaneous B-cell lymphomas.

A membrane-disrupting peptide derived from the influenza virus was covalently linked to different polymethacrylates (pDMAEMA, pDAMA and the degradable pHPMA-DMAE, monomers depicted in Fig. 1) using N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) as coupling agent to increase the transfection efficiency of polyplexes based on these polymers. It was shown by circular dichroism (CD) measurements that the polymer-conjugated peptide was, as the free peptide, able to undergo a conformational change of a random coil to an alpha helix upon lowering the pH to 5.0. This indicates that the property of the peptide to destabilize the endosomal membrane was preserved after its conjugation to the cationic polymers. In line herewith, a liposome leakage assay revealed that the polymer-bound peptide has comparable activity as the free peptide. The DNA condensing properties of the synthesized polymer-peptide conjugates were studied with dynamic light scattering and zeta-potential measurements, and it was shown that small (100 to 250 nm), positively charged (+15 to +20 mV) particles were formed. In vitro transfection and toxicity was tested in COS-7 cells, and these experiments showed that the polyplexes with grafted peptide had a substantially higher transfection activity than the control polyplexes, while the toxicity remained unchanged. Cellular uptake of the polyplexes was visualized with confocal laser scanning microscopy, and no differences in cellular uptake could be determined between the peptide containing systems and the control formulation. This shows that the increased transfection activity is indeed due to a better endosomal escape of the peptide grafted polyplexes. This study demonstrates that it is possible to covalently conjugate an endosome disruptive peptide to cationic gene delivery polymers with preservation of its membrane destabilization activity, making these conjugates suitable for in vivo DNA delivery.

A cationic polymethacrylate with a guanidinium side group was designed in order to create a polymer with cell membrane-penetrating properties such as Tat or other arginine-rich peptides. The polymer, poly(3-guanidinopropyl methacrylate), abbreviated as pGuaMA, was synthesized by free radical polymerization. The DNA-condensing properties of pGuaMA (Mw 180 kDa) were investigated via dynamic light scattering and zeta potential measurements, and small, positively charged particles (110 nm, +37 mV) were found. It was shown that polyplexes based on pGuaMA were able to transfect COS-7 cells efficiently in the absence of serum, while under the same conditions poly(arginine) (pArg) polyplexes did not show detectable transfection levels. Addition of a membrane-disrupting peptide, INF 7, derived from the influenza virus, to preformed pGuaMA polyplexes did result in approximately 2 times increased transfection levels. DLS, zeta potential measurements, gel electrophoresis, and ethidium bromide displacement measurements indicated that serum induced aggregation of the polyplexes at high polymer/plasmid ratios, while at low polymer/plasmid ratios the polarity of the polyplexes reversed likely due to adsorption of negatively charged proteins on their surface. Likely, the unfavorable interactions of pGuaMA polyplexes with serum proteins is the reason for the absent transfection activity of these polyplexes in the presence of serum. Confocal laser scanning microscopy indicated cellular internalization via endocytosis of both polyplexes and free polymer. Thus, pGuaMA polyplexes enter cells, as reported for other polyplexes, by endocytosis and not, as hypothesized, via direct membrane passage.

What do you see Walt Whitman? Who are they you salute, and that one after another salute you? ... I see the curious rapid change of the light and shade, I see distant lands, as real and near to the inhabitants of them as my land is to me ... All you continentals of Asia, Africa, Europe, Australia, indifferent of place! All you on the numberless islands of the archipelagoes of the sea! And you of centuries hence when you listen to me! And you each and everywhere whom I specify not, but include just the same! Health to you! good will to you all, from me and America sent! Each of us inevitable, Each of us limitless--each of us with his or her rights upon the earth, Each of us allow'd the eternal purports of the earth, Each of us here as divinely as any is here. --From Walt Whitman, "Salut Au Monde" In July 2001, Veronica Makowsky invited us to guest-edit a special issue of MELUS in celebration of Katharine Dealy Newman's life and work. We knew then already that our festschrift for Newman would have to be more than just a miscellaneous volume to honor the memory of the woman who had played a more crucial role than any other individual in bringing MELUS--and MELUS--into existence in the early 1970s. Imbued strongly with what we know today as the MELUS mission, Katharine herself would have liked such a celebration to be more than a compendium of her life and achievements. So we decided in our Call to spread our net as wide as possible to attract scholarly fish of all hues, and see what we could gather. Our Call stated in part, "Our objective in bringing out this special number is to preserve and expand Newman's legacy by attempting a retrospective evaluation of the role played by MELUS during the past three decades in the ongoing re-definition of American Literature by taking stock of developments in ethnic and cultural studies since the 1960s." We welcomed especially essays on pedagogy, canon, theory, and ethnic literary studies as a "discipline," as well as others on the role of anthologies and critical editions in transforming curriculum. We had also hoped to include some new interpretations of by-now canonical ethnic American authors or texts, as well as some pieces dedicated to the recovery of lost, neglected, and forgotten figures or texts. As our table of contents indicates, we have every reason to be happy with the wide-ranging response from our fellow scholars. To be sure, like the persona in that elusive Emerson poem, "Days," we might acknowledge the understandable gap between what one wishes for and what one actually receives. And yet, this gathering of essays by Americanists from around the globe, seasoned and emerging scholars as well as graduate students still discovering their voices, represents some of the most exciting scholarship in US literary studies on issues of canon and context, pedagogy and theory, race and ethnicity, gender and sexuality, nation and diaspora, individual and group identity. We are especially pleased to include quite a few international scholars: from Ireland, Germany, India, Italy, Poland, and Israel. We expect that this collection as a whole, and through its individual essays, will raise new debate and discussion, and for us, that is indeed the best measure of how we might remember Newman and honor her legacy. In relation to the many shared spaces and intersections among the interconnected and overlapping areas of American Studies and Cultural Studies, multi-ethnic literary studies as a field--in tandem with African American literary studies--is now so vast that it would be foolhardy for any one volume to cover all its subsets systematically and exhaustively. While limited in many ways by what we could accept from the submissions we received--or at times, what we could nudge or commission into being to fill up some lacunae--we were attentive to the need to cover a wide and suggestive range of issues in relation to the multiple ethnicities and historical experiences that make up the United States and the Americas beyond. …

In hybrid environments, where real and virtual overlap, participants naturally see, touch, and manipulate the object at hand.

Resume Propos. – Les inhibiteurs d'enzyme de conversion de l'angiotensine (IEC) sont utilises depuis une vingtaine d'annees, et constituent un reel progres dans la prise en charge de l'hypertension arterielle ou de l'insuffisance cardiaque. Leur tolerance est en general bonne et la toux constitue l'effet indesirable le plus frequent. L'angio-œdeme realise un œdeme localise et soudain des tissus sous-cutanes et des muqueuses et surviendrait chez 0,1 a 0,5 % des patients sous IEC. Methodes. – Nous rapportons 19 cas d'angio-œdeme apres prise d'IEC repertories au centre regional de pharmacovigilance d'Amiens. Resultats. – La face est une localisation constante chez les 19 patients de notre serie. Plus trompeuses peuvent etre les localisations aux muqueuses digestives (1 cas) ou genitales (1 cas). Le delai d'apparition est variable, immediat dans un tiers des cas, retarde apres plusieurs annees dans un autre tiers. La survenue d'une atteinte laryngee peut etre responsable de deces (1 cas). Conclusion. – Le mecanisme physiopathologique est actuellement inconnu. Il pourrait dependre d'une accumulation de bradykinine. Le traitement impose l'arret definitif de tout IEC. Les antagonistes des recepteurs de l'angiotensine II peuvent etre une alternative mais doivent etre introduits avec precaution.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Phacoemulsification is the main gold standard for cataract operation in the developed world together with foldable intraocular lens (IOL) implantation by injection, allowing for stable wound construction and less postoperative astigmatism. It is a safe procedure with high success rate with the advancement in machines, improvement of IOL injection systems and further maturation of surgeons' techniques. Despite the large number of operations performed every day, foldable IOL injection leading to an intra-stromal corneal track is a very rare complication. We report a case of this unusual finding in a 70-year-old gentleman who has undergone cataract operation in November 2011 in our hospital and will review on the complications related to foldable IOL injection.

Crohn's disease is a chronic inflammatory intestinal pathology which can be associated to different extra-digestive manifestations. We reported a case of recurrent genital lymphedema leading to Crohn's disease diagnosis.A 49-year-old man was referred for increased penis and scrotal volume, associated with recurrent febrile flare during the 10 previous years. Clinically, we noted an inflammatory penis and scrotum lymphedema. Clinical urological examination, and biological, bacteriological, computer-tomography examinations were negative. Metastatic Crohn's disease was diagnosed in association with concomitant severe terminal ileitis. Treatment with corticosteroids and azathioprine resulted in significant decrease of inflammatory genital lymphedema.Genital inflammatory lymphedema occurs during inflammatory, infectious, and tumor diseases. Some cases of metastatic genital lymphedema related to Crohn's disease are described, most often in children. Inflammatory genital lymphedema associated with gastrointestinal symptoms may suggest Crohn's disease.

Summary Background Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies. Objectives To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24). Methods A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up. Results In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36·8 ± 55·5 cm2 and 24·8 ± 45·7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0·001), adherence to compression therapy at W4 (P = 0·03) and W24 (P = 0·01), ankle-joint ankylosis (P = 0·01) and mean percentage of VLU area reduction at W4 (P = 0·04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8·4, 95% confidence interval (CI) 1·9–48·2] and percentage reduction of the VLU area at W4 (OR 1·6, 95% CI 1·0–2·14) as being independently associated with healing. Conclusions These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment.

Les lymphoproliferations post-transplantation d’organes solides (LPTOS) representent la troisieme cause de tumeurs apres les cancers cutanes et la maladie de Kaposi avec une incidence pouvant aller jusqu’a 10 % selon l’organe transplante. Les LPTOS purement cutanees sont rares avec moins de 100 cas publies dans la litterature, cependant leur incidence semble progresser depuis plusieurs annees.

Background The treatment of stage I Merkel cell carcinoma (MCC) usually includes wide local excision (WLE) combined with irradiation of the tumor bed (ITB). No randomized study has ever been conducted in MCC. The purpose of this study was to assess the efficacy and safety of prophylactic adjuvant radiotherapy on the regional nodes. Patients and methods In this randomized open controlled study, patients for a stage I MCC treated by WLE and ITB were randomly assigned to regional adjuvant radiotherapy versus observation. Overall survival (OS) and probability of regional recurrence (PRR) were primary end points. Progression-free survival (PFS) and tolerance of irradiation were secondary end points. Results Eighty-three patients were included before premature interruption of the trial, due to a drop in the recruitment mainly due to the introduction of the sentinel node dissection in the management of MCC. No significant improvement in OS (P = 0.989) or PFS (P = 0.4) could be demonstrated after regional irradiation, which, however, significantly reduced the PRR (P = 0.007) with 16.7% regional recurrence rate in the observation arm versus 0% in the treatment arm. The treatment was well tolerated. Conclusion The adjuvant regional irradiation significantly decreased the PRR in MCC, but benefit in survival could not be demonstrated.

The data concerning changes in the characteristics of hypertensive leg ulcers (HLU) were taken from open studies in a small patient cohort. The aim of this study was to describe the epidemiological characteristics and to identify prognostic factors for healing in a prospective cohort of 59 patients presenting HLU.The cohort comprised patients included in a randomized, double-blind, controlled study published elsewhere; the patients were receiving becaplermin gel (Regranex(®)) or Duoderm Hydrogel™ once daily for eight weeks for the most recent wound. Total follow-up was 12 weeks.The epidemiological analysis was performed for 59 consecutive patients randomized in 17 dermatology departments. Mean patient age was 74.5 ± 9 years and 61% were female. Mean wound duration was 11.1 ± 9 weeks and median wound area was 16 cm(2) (q1; q3: 8; 25.5). Among, 94.9% of patients had hypertension and 39.7% were diabetic. A homolateral peripheral pulse was present in 91.5% of patients. At the end of follow-up, complete wound healing was obtained in 30.5% of the patients. In univariate analysis, neither the foregoing criteria nor the treatment group were significantly associated with healing during the study.This study confirms female predominance, old age, prevalence of diabetes and delay in the diagnosis of HLU. The prognosis for healing does not appear to be dependent on wound duration, wound area or the presence of moderate peripheral arterial disease, doubtless because this condition progresses by episodes of flare-up and under specific conditions.

Eosinophilic dermatosis of hematologic disease (EDH) or insect bite-like reaction is a pruritic dermatitis described mostly in patients with chronic lymphocytic leukaemia (CLL). We describe six patients with the disorder in association with CLL and other blood dyscrasias.We reviewed the medical records of patients with EDH seen between 2004 and 2009 in our department and re-examined histological slides.Mean age at dermatosis onset was 75.6 years and the sex ratio was 1. There were three CLL, two mantle-cell lymphomas and one MALT-type lymphoma. The dermatitis was quite polymorphic, with erythematous papules, wheals and plaques. The initial skin lesions appeared at the same time as or after the diagnosis of haematological neoplasm. Their reappearance heralded relapse of the blood disease in three cases. Histologically, all lesions had a dense dermal infiltrate of small, mostly CD4+ T-cells, with numerous eosinophils. In three patients, there was marked folliculotropism, resembling folliculotropic T-cell lymphoma. In most cases, EDH disappeared after appropriate chemotherapy for the blood disorder.Our cases show that the clinical expression of EDH is quite polymorphic. Its appearance may precede relapse of or may indicate prompt search screening for blood dyscrasia. The most efficient treatment of this dermatosis appears to be specific chemotherapy for the blood dyscrasia. There is reason to believe that a population of T-helper 2 (Th2) lymphocytes, reactive to malignant B-cells, induces tissue eosinophilia, mainly through production of interleukin (IL)-5, among other cytokines. Eosinophils appear to be the main effector cells.

Bortezomib (Velcade) is a proteasome inhibitor used in the treatment of myeloma and other blood dyscrasias. We report the cases of two patients who developed a peculiar toxic rash suggestive of Sweet's syndrome while receiving bortezomib; one patient also presented giant mucous membrane ulcerations.Case 1: bortezomib treatment was started in a 62-year-old man for mantle cell lymphoma. Ten days after the first treatment cycle, giant, painful oral ulcerations were noted but they resolved spontaneously. One week after the second cycle, further oral ulceration appeared, this time with a papulonodular skin rash. Histology showed neutrophilic dermal infiltrates in the skin with predominantly lymphocytic inflammation of the oral mucosa. Bortezomib was stopped and all lesions resolved with colchicine treatment. Case 2: a 46-year-old woman was receiving bortezomib treatment for plasma cell leukemia. A febrile skin rash appeared two days after the first treatment cycle but resolved spontaneously. After the first bortezomib injection during the next cycle, painful papules and nodules appeared on the trunk. The skin biopsy results were consistent with Sweet's syndrome. The lesions disappeared spontaneously. Dexamethasone was administered concomitantly with bortezomib in the ensuing cycles and there was no relapse of the skin lesions.Bortezomib-induced skin lesions are common and usually do not justify treatment withdrawal. Published observations of bortezomib-induced eruption occasionally show clinical and histological features of Sweet's syndrome, but there has been no mention of oral mucosal ulcerations. In our cases, these could be related to bortezomib-induced neutrophilic dermatosis.

Heparin-induced bullous hemorrhagic dermatosis is a rare, recently described side-effect of subcutaneous heparin injection. We describe a patient simultaneously presenting distant haemorrhagic bullae and eczematous reaction at the low molecular-weight heparin (LMWH) injection sites.Subcutaneous enoxaparin sodium was initiated in a 51-year-old patient and was replaced a few days later by tinzaparin sodium. Forty-eight hours later, annular, erythematous and vesicular plaques appeared at the injection sites (thighs). Small hemorrhagic bullae were noted on the abdominal skin at the same time. Skin biopsies revealed respectively eczematous dermatitis and an intraepidermal blister filled with red blood cells. Direct immunofluorescence was negative. Standard laboratory investigations and coagulation studies were unremarkable. Skin lesions disappeared ten days after discontinuation of LMWH. Patch tests and intradermal tests were negative.The case described herein shares the stereotypical clinical picture previously reported, namely small, multiple, haemorrhagic bullae on normal skin, appearing at remote sites five to 21 days after the start of subcutaneous heparin treatment. Despite the absence of clear management guidelines, it is obviously tempting to stop the heparin if there are too many bullae for fear of more clinically significant and dangerous mucous membrane lesions. The underlying physiopathological mechanism is poorly understood; no coagulation abnormalities were recorded. In addition, our patient presented an eczematous reaction at the injection sites, raising the possibility of a type IV hypersensitivity reaction. The association of these two cutaneous side effects of heparin is perhaps not purely coincidental.

Bioreducible poly(amido amine)s (SS-PAAs) with different groups in the side chain were evaluated for gene delivery to ovarian cancer cells, both in vitro and in vivo after intraperitoneal administration in mice bearing an ovarian cancer xenograft. Polyplexes of SS-PAAs with e.g. hydroxybutyl or hydroxypentyl side groups induce much higher transfection in vitro than polyplexes of branched pEI (25 kDa) as a positive control. The in vivo transfection efficiency of polyplexes of SS-PAA with hydroxybutyl side groups is similar to that of linear pEI (22 kDa).

To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery properties, a series of poly(amido amine) (co)polymers were synthesized by Michael addition polymerization of N, N'-cystaminebisacrylamide with variable ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH(2)), and tert-butyl-4-aminobutyl carbamate (BocNH-BuNH(2)), yielding poly(amido amine)s (NicX-NHBoc) with X=0, 10, 30, and 50 % of quaternary nicotinamide groups in the polymer side chains. Deprotection of the pendant Boc-NH groups afforded an analogous series of polymers (NicX-NH(2)) with higher charge density (due to the presence of protonated primary amino groups in the side chains) and subsequent acetylation yielded a series of polymers (NicX-NHAc) of lower hydrophobicity than the Boc-protected polymers. The polymers with the Boc-protected or the acetylated amino groups showed high buffer capacity in the range pH 5.1-7.4, which is a property that can contribute to endosomal escape of polyplexes. The presence of quaternary nicotinamide groups has distinct beneficial effects on the gene vector properties of these polymers. The polymers containingor=30 % of quaternary nicotinamide groups in their side chains condense DNA into small, nanosized particles (or=200 nm) with positive surface charge (or=+15 mV). Fluorescence experiments using ethidium bromide as a competitor showed that the quaternary nicotinamide groups intercalate with DNA, contributing to a more intimate polymer-DNA binding and shielding. Polyplexes of nicotinamide-functionalized poly(amido amine)s NicX-NHBoc and NicX-NHAc, formed at 12/1 polymerDNA mass ratio, efficiently transfect COS-7 cells with efficacies up to four times higher than that of PEI (Exgen 500), and with essentially absence of cytotoxicity. NicX-NH(2) polymers, possessing protonated primary amino groups in their side chains, have a higher cytotoxicity profile under these conditions, but at lower 3/1 polymer-DNA mass ratio also these polymers are capable of efficient transfection, while retaining full cell viability.

A new cationic biodegradable polyphosphazene was developed, bearing both pendant primary and tertiary amine side groups, poly(2-dimethylaminoethylamine-co-diaminobutane)phosphazene (poly(DMAEA-co-BA)phosphazene). PEG and PEG-folate were coupled to polyplexes based on this poly(DMAEA-co-BA)phosphazene, leading to small (size 100 and 120 nm, respectively) and almost neutral particles. In vitro tissue culture experiments showed a low cytotoxicity of both uncoated and coated polyplexes. However, the PEG coated polyplexes showed a 2-fold lower transfection activity in OVCAR 3 cells as compared to the uncoated polyplexes. On the other hand, the PEG-folate coated polyplexes had a 3-fold higher transfection than the PEGylated polyplexes. When free folate was added to the transfection medium, only the transfection activity of the targeted polyplexes was reduced, indicating internalization of the targeted PEG polyplexes via the folate receptor. Confocal laser scanning microscopy confirmed a lower binding and uptake of the PEGylated polyplexes by OVCAR-3 cells when compared to uncoated and folate-PEGylated polyplexes. While uncoated polyplexes induced aggregation of erythrocytes at polymer concentrations of 0.09 μg/mL, the PEGylated systems could be incubated at ten times higher concentration before aggregation occurred indicating excellent shielding of the surface charge of the polyplexes by grafting of PEG. In conclusion, the targeted delivery of poly(DMAEA-co-BA)phosphazene bases polyplexes and their improved compatibility with erythrocytes makes them interesting for in vivo applications.

Mycophenolate sodium (Myfortic) is an enteric-coated formulation of the immunosuppressant therapy mycophenolic acid. We report a case of diffuse mouth ulceration in a patient treated with Myfortic presenting recurrence after another dose of drug.We report the case of a 26-year-old female patient with systemic lupus erythematosus, initially treated with corticosteroids and mycophenolate mofetil, but which was stopped because of varicella-zoster dissemination and leucopoenia. She consulted for mouth ulcers occurring two weeks after the introduction of Myfortic. There were no signs of opportunist infection or lupus activity. Mucosal ulcerations disappeared when Myfortic was stopped. Several weeks later, the patient presented recurrence of mouth ulcerations after another treatment of Myfortic.Myfortic is a new enteric-coated formulation of mycophenolic acid developed to reduce gastrointestinal upset associated with Cellcept. In certain cases, Cellcept toxicity can present as a number of oral ulcerations. Direct toxicity is involved in these cases. This side effect has never been described with Myfortic. In our case, the distinctive characteristic is that the patient was never treated with Cellcept without mucosal toxicity despite equivalent systemic mycophenolic acid exposure.

Poly(amido amine) (SS-PAA) random and block copolymers having bioreducible disulfide bonds in the main chain and amino groups with distinctly different basicity in the side chain were designed and synthesized by Michael addition polymerization between N, N′-cystaminebisacrylamide (CBA) and two amine monomers, i.e., histamine (HIS) and 3-(dimethylamino)-1-propylamine (DMPA). Copolymers containing variable HIS/DMPA ratios show higher ability to bind DNA than p(CBA-HIS) homopolymer and condense DNA into the polyplexes with particle sizes (< 150 nm) that are smaller than polyplexes of p(CBA-HIS) (not, vert, similar 220 nm). The buffer capacities of the copolymers increase with increasing HIS/DMPA ratio. These copolymers are able to transfect COS-7 cells in vitro with efficiencies that increase with increasing HIS/DMPA ratio. The random and block copolymers at a HIS/DMPA ratio of 70/30 combines optimal DNA condensation capability and buffer capacity, thereby inducing higher transfection efficiency in the absence and presence of serum as compared to p(CBA-HIS) homopolymer. Moreover, random and block copolymers show a similar transfection capacity, but both have higher capacity than the physical mixtures of p(CBA-HIS) and p(CBA-DMPA) homopolymers. XTT assay reveals that the polyplexes of the SS-PAA copolymers have essentially low cytotoxicity when the highest transfection activity is observed.

Lhermitte-Duclos disease, or dysplastic cerebellar gangliocytoma is a rare entity characterized by a hamartomatous lesion in the posterior fossa. Cowden's syndrome, or hamartoma-neoplasia syndrome is a rare underdiagnosed autosomal dominant genodermatosis with high incidence of malignant tumors. Several recent reports suggest that Lhermitte-Duclos disease may be a component of Cowden's syndrome.We report two cases of Lhermitte-Duclos and Cowden disease occurring in adult patients. A 40-year-old woman had symptoms of raised intracranial pressure and macrocephaly. She displayed the stigmata of fibrocystic breast disease, thyroid goitre. Clinical examination showed mucocutaneous lesions. Her mother, brother and uncle had manifestations of Cowden's disease. An asymptomatic 38-year-old male had bilateral optic nerve drusen related to a cerebellar neoplasm. He exhibited manifestations of Cowden's syndrome and his familial history confirmed this hypothesis.The first patient was operated on for Lhermitte-Duclos disease. A conservative strategy was performed for the second patient and the clinical and imaging follow-ups were uneventful over 5 years.We stress the possibility that Lhermitte-Duclos and Cowden disease might be a peculiar form of phakomatosis. A conservative strategy can be chosen without neurological signs because of slow tumor growth. However, these patients should be carefully examined and followed up because of the risk of future malignancy.

Imatinib (Gleevec) is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia. We describe a case of drug reaction with eosinophilia and systemic symptoms (DRESS) after institution of treatment with imatinib.A 78-year-old woman was treated with low-dose imatinib for chronic myeloid leukemia since November 2003. A macular and pruritic eruption appeared on the patient's trunk after 7 weeks of treatment and gradually worsened. After 1 month, she was admitted for generalized skin eruption with fever and diffuse lymphadenopathy. Laboratory data showed hypereosinophilia and blood cultures positive for Staphylococcus aureus. Imatinib was stopped and replaced with hydroxyurea (Hydrea). Improved clinical and laboratory results were seen with antibiotics and topical steroids.To our knowledge, this is the first case of DRESS following treatment with imatinib. Cutaneous reactions to imatinib are frequent and are usually mild, comprising maculopapular eruption, pruritus and facial edema. Few cases of serious skin reactions have been reported until now. Several authors suggest that the prevalence and severity of cutaneous manifestations are related to a pharmacologic effect of imatinib. Our observation cannot rule out an underlying immunologic mechanism. Septicemia may also play a part in the development of DRESS.

The ability to efficiently produce hundreds of proteins in parallel is the most basic requirement of many aspects of proteomics. Overcoming the technical and financial barriers associated with high throughput protein production is essential for the development of an experimental platform to query and browse the protein content of a cell (e.g. protein and antibody arrays). Proteins are inherently different one from another in their physicochemical properties; therefore, no single protocol can be expected to successfully express most of the proteins. Instead of optimizing a protocol to express a specific protein, we used sequence analysis tools to estimate the probability of a specific protein to be expressed successfully using a given protocol, thereby avoiding a priori proteins with a low success probability. A set of 547 proteins, to be used for antibody production and selection, was expressed in Escherichia coli using a high throughput protein production pipeline. Protein properties derived from sequence alone were correlated to successful expression, and general guidelines are given to increase the efficiency of similar pipelines. A second set of 68 proteins was expressed to investigate the link between successful protein expression and inclusion body formation. More proteins were expressed in inclusion bodies; however, the formation of inclusion bodies was not a requirement for successful expression.

Association of malignant cutaneous tumor and secondary anetoderma is rare. Secondary anetoderma in myxofibrosarcoma has not been described to date. We report a case below.A 80-year-old woman presented with a 40 x 40 mm, round, flesh-colored lesion on her left buttock. Physical examination showed a soft, protuberant lesion, without firm underlying subcutaneous mass. Pathologic examination of the surgical specimen revealed a myxofibrosarcoma, with focal loss of elastic fibers in the overlying dermis. There was no evidence of systemic involvement. One year later, she developed a recurrent tumor at the same site, with similar clinical presentation, which was treated by broad excision.Secondary anetoderma is usually seen in association with cutaneous infections and benign skin tumors. An anetodermic presentation of myxofibrosarcoma has not been reported to our knowledge. Myxofibrosarcoma (formerly referred to as myxoid malignant fibrous histiocytoma) is characterized by an abundant myxoid background in at least one half of the tumor. The tumor recurs in almost two-thirds of cases and metastasizes in one-fourth. Our case confirms that a unique, acquired anetodermic lesion can reveal a malignant tumor. A large deep biopsy should be performed systematically when this variety of anetoderma is observed.