Pyoderma gangrenosum after totally implanted central venous access device insertion

<p>Abstract</p> <p>Background</p> <p>Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form of pyoderma gangrenosum is characterized by a rapidly progressing painful irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma gangrenosum remains unclear. In about 70% of cases, it is associated with a systemic disorder, most often inflammatory bowel disease, haematological disease or arthritis. In 25–50% of cases, a triggering factor such as recent surgery or trauma is identified. Treatment consists of local and systemic approaches. Systemic steroids are generally used first. If the lesions are refractory, steroids are combined with other immunosuppressive therapy or to antimicrobial agents.</p> <p>Case presentation</p> <p>A 90 years old patient with myelodysplastic syndrome, seeking regular transfusions required totally implanted central venous access device (Port-a-Cath^®) insertion. Fever and inflammatory skin reaction at the site of insertion developed on the seventh post-operative day, requiring the device's explanation. A rapid progression of the skin lesions evolved into a circular skin necrosis. Intravenous steroid treatment stopped the necrosis' progression.</p> <p>Conclusion</p> <p>Early diagnosis remains the most important step to the successful treatment of pyoderma gangrenosum.</p

Impact of Age and Body Site on Adult Female Skin Surface pH

Background: pH is known as an important parameter in epidermal barrier function and homeostasis. Aim: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. Methods: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 +/- 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. Results: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. Conclusion: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products. Copyright (C) 2012 S. Karger AG, Base

A phase i study of daily treatment with a ceramide-dominant triple lipid mixture commencing in neonates

<p>Abstract</p> <p>Background</p> <p>Defects in skin barrier function are associated with an increase risk of eczema and atopic sensitisation. Ceramide-dominant triple lipid mixture may improve and maintain the infant skin barrier function, and if shown to be safe and feasible, may therefore offer an effective approach to reduce the incidence of eczema and subsequent atopic sensitisation. We sort to assess the safety and compliance with daily application of a ceramide-dominant triple lipid formula (EpiCeram™) commencing in the neonatal period for the prevention of eczema.</p> <p>Methods</p> <p>Ten infants (0-4 weeks of age) with a family history of allergic disease were recruited into an open-label, phase one trial of daily application of EpiCeram™ for six weeks. The primary outcomes were rate of compliance and adverse events. Data on development of eczema, and physiological properties of the skin (transepidermal water loss, hydration, and surface pH) were also measured.</p> <p>Results</p> <p>Eighty percent (8/10) of mothers applied the study cream on 80% or more of days during the six week intervention period. Though a number of adverse events unrelated to study product were reported, there were no adverse skin reactions to the study cream.</p> <p>Conclusions</p> <p>These preliminary results support the safety and parental compliance with daily applications of a ceramide-dominant formula for the prevention of eczema, providing the necessary ground work for a randomised clinical trial to evaluate EpiCeram™ for the prevention of eczema.</p> <p>Trial registration</p> <p>The study was listed at the Australian/New Zealand Clinical Trial Registry (ANZCTR): reg. no. <a href="http://www.anzctr.org.au/ACTRN12609000727246.aspx">ACTRN12609000727246</a>.</p

Outcome of Occupational Latex Allergy—Work Ability and Quality of Life

OBJECTIVE: The quality of life (QOL) and work ability of health care workers allergic to natural rubber latex (NRL) were assessed after implementation of regulations on powder-free NRL gloves in Germany. METHODS: 196 HCW with reported NRL allergy answered a questionnaire (response rate 58%) containing the Work Ability Index (WAI), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), and Dermatology Life Quality Index (DLQI). RESULTS: 63.2% still had NRL-related symptoms during the last 6 month. However on a scale from 0 to 10, the intensity of NRL-related symptoms decreased from 8.5 before to 2.3 after implementation of regulations on powder-free NRL gloves. A higher number of subjects were able to avoid NRL in the private than in the work environment (85% vs. 61%). NRL-related symptoms decreased and WAI increased with successful avoidance of NRL at workplace (b = 0.23, p = 0.003). QOL was only little affected by NRL allergy (mean: MiniAQLQ = 6.0; DLQI = 4.1). CONCLUSIONS: Although there was improvement after implementation of powder-free NRL gloves, there is still a considerable number of HCW with NRL-related symptoms. Further investigations on latex avoidance and the cause of persisiting allergic symptoms in HCW with NRL allergy are therefore needed

DNA Damage Triggers Genetic Exchange in Helicobacter pylori

Many organisms respond to DNA damage by inducing expression of DNA repair genes. We find that the human stomach pathogen Helicobacter pylori instead induces transcription and translation of natural competence genes, thus increasing transformation frequency. Transcription of a lysozyme-like protein that promotes DNA donation from intact cells is also induced. Exogenous DNA modulates the DNA damage response, as both recA and the ability to take up DNA are required for full induction of the response. This feedback loop is active during stomach colonization, indicating a role in the pathogenesis of the bacterium. As patients can be infected with multiple genetically distinct clones of H. pylori, DNA damage induced genetic exchange may facilitate spread of antibiotic resistance and selection of fitter variants through re-assortment of preexisting alleles in this important human pathogen

Identification of a Putative Crf Splice Variant and Generation of Recombinant Antibodies for the Specific Detection of Aspergillus fumigatus

BACKGROUND: Aspergillus fumigatus is a common airborne fungal pathogen for humans. It frequently causes an invasive aspergillosis (IA) in immunocompromised patients with poor prognosis. Potent antifungal drugs are very expensive and cause serious adverse effects. Their correct application requires an early and specific diagnosis of IA, which is still not properly achievable. This work aims to a specific detection of A. fumigatus by immunofluorescence and the generation of recombinant antibodies for the detection of A. fumigatus by ELISA. RESULTS: The A. fumigatus antigen Crf2 was isolated from a human patient with proven IA. It is a novel variant of a group of surface proteins (Crf1, Asp f9, Asp f16) which belong to the glycosylhydrolase family. Single chain fragment variables (scFvs) were obtained by phage display from a human naive antibody gene library and an immune antibody gene library generated from a macaque immunized with recombinant Crf2. Two different selection strategies were performed and shown to influence the selection of scFvs recognizing the Crf2 antigen in its native conformation. Using these antibodies, Crf2 was localized in growing hyphae of A. fumigatus but not in spores. In addition, the antibodies allowed differentiation between A. fumigatus and related Aspergillus species or Candida albicans by immunofluorescence microscopy. The scFv antibody clones were further characterized for their affinity, the nature of their epitope, their serum stability and their detection limit of Crf2 in human serum. CONCLUSION: Crf2 and the corresponding recombinant antibodies offer a novel approach for the early diagnostics of IA caused by A. fumigatus

The Extended Cleavage Specificity of Human Thrombin

Thrombin is one of the most extensively studied of all proteases. Its central role in the coagulation cascade as well as several other areas has been thoroughly documented. Despite this, its consensus cleavage site has never been determined in detail. Here we have determined its extended substrate recognition profile using phage-display technology. The consensus recognition sequence was identified as, P2-Pro, P1-Arg, P1′-Ser/Ala/Gly/Thr, P2′-not acidic and P3′-Arg. Our analysis also identifies an important role for a P3′-arginine in thrombin substrates lacking a P2-proline. In order to study kinetics of this cooperative or additive effect we developed a system for insertion of various pre-selected cleavable sequences in a linker region between two thioredoxin molecules. Using this system we show that mutations of P2-Pro and P3′-Arg lead to an approximate 20-fold and 14-fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200–400 times, which highlights the importance of these two positions for maximal substrate cleavage. Interestingly, no natural substrates display the obtained consensus sequence but represent sequences that show only 1–30% of the optimal cleavage rate for thrombin. This clearly indicates that maximal cleavage, excluding the help of exosite interactions, is not always desired, which may instead cause problems with dysregulated coagulation. It is likely exosite cooperativity has a central role in determining the specificity and rate of cleavage of many of these in vivo substrates. Major effects on cleavage efficiency were also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 resulted in a drop in cleavage by a factor of almost 20 times

Diagnosis of invasive candidiasis in the ICU

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment

Skin Barrier Homeostasis in Atopic Dermatitis: Feedback Regulation of Kallikrein Activity

Atopic dermatitis (AD) is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema) to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs), whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical) stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier in AD and healthy individuals