Comparison of Transepidermal Water Loss and Laser Scanning Microscopy Measurements to Assess Their Value in the Characterization of Cutaneous Barrier Defects

The exact qualitative and quantitative analysis of wound healing processes is a decisive prerequisite for optimizing wound care and for therapy control. Transepidermal water loss (TEWL) measurements are considered to be the standard procedure for assessing the progress of epidermal wound healing. The damage to the stratum corneum correlates with an increased loss of water through the skin barrier. This method is highly susceptible to failure by environmental factors, in particular by temperature and moisture. This study was aimed at comparing TEWL measurements and in vivo laser scanning microscopy (LSM) for the characterization of the epidermal wound healing process. LSM is a high-resolution in vivo method permitting to analyze the kinetics and dynamics of wound healing at a cellular level. While the TEWL values for the individual volunteers showed a wide scattering, LSM permitted the wound healing process to be clearly characterized at the cellular level. However, a comparison between the two methods was very difficult, because the results provided by LSM were images and not numerical. Therefore, a scoring system was set up which evaluates the stages of wound healing. Thus, the healing process could be numerically described. This method is independent of any environmental factors. Providing morphologically qualitative and numerically quantitative analyses of the wound healing process and being far less vulnerable to failure, LSM is advantageous over TEWL

Evaluation of efalizumab using safe psoriasis control

BACKGROUND: Safe Psoriasis Control (SPC) is an important comprehensive measure that is validated for the assessment of benefit:risk of psoriasis treatments, combining efficacy, quality of life, and safety measures. The objective of this analysis was to assess the benefit:risk of efalizumab, a novel biologic agent indicated for the treatment of moderate-to-severe plaque psoriasis, by applying the SPC to data from randomized, placebo-controlled clinical studies of efalizumab. METHODS: SPC was applied to week 12 data from four placebo-controlled, Phase III studies: three retrospective and one prospective, the latter including a cohort of "high-need" patients for whom existing therapies were inadequate or unsuitable. RESULTS: In the retrospective analysis, 39.4% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 10.4% for placebo. In the prospective analysis, 34.3% of patients achieved SPC after 12 weeks of treatment with efalizumab, compared with 7.3% on placebo. Among high-need patients, 33.0% achieved SPC, compared with 3.4% on placebo. CONCLUSION: Efalizumab has a favorable benefit:risk profile using the comprehensive outcome measure SPC

The long-term efficacy and safety of new biological therapies for psoriasis

Long-term therapy is often required for psoriasis. This article reviews the most recent long-term clinical data for biological agents that have been approved or for which late-stage development data have been released for the treatment of patients with moderate to severe plaque psoriasis. Efficacy data are available for up to five 12-week courses of alefacept (approximately 60 weeks of therapy), 36 months (144 weeks) of continuous efalizumab, 48 weeks of continuous etanercept, and 50 weeks of bimonthly infliximab. Data sources include publications, product labeling, and posters presented at recent international scientific meetings. Alefacept appears to continue to be efficacious over multiple treatment courses for some responsive patients. The efficacy of efalizumab achieved during the first 12–24 weeks of therapy appears to be maintained or improved through at least 60 weeks of continuous treatment. The efficacy of etanercept appears to be maintained through at least 48 weeks of continuous treatment. Infliximab demonstrates a high response rate soon after initiation, which appears to be maintained through 24 weeks but declines modestly with therapy out to 50 weeks. After 48 weeks, approximately 60% of efalizumab-treated and 45% of etanercept-treated patients remaining on therapy achieved ≥75% improvement from baseline in Psoriasis Area and Severity Index, as did 70.5% of infliximab patients who did not miss more than two infusions. Safety data suggest that these agents may be used for long-term administration. Long-term data from psoriasis trials continue to accumulate. Recent data suggest that biological therapies have efficacy and safety profiles suitable for the long-term treatment of patients with moderate to severe psoriasis

Guidelines on the use of extracorporeal photopheresis

Peer reviewe

Fixed-time artificial insemination in beef cattle

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The study was designed to test the effect of fixed-time artificial insemination (fixed-AI) after the slightly modified Ovsynch protocol on the pregnancy rate in beef cattle in Finnish field conditions. The modification was aimed to optimize the number of offsprings per AI dose. Methods: Ninety Charolais cows and heifers were entered into the program an average of 1.8 times. Thus, 164 animal cases were included. Animals were administered 10-12 μg of buserelin. Seven days later animals without a corpus luteum (CL) were rejected (20.7%) while the remaining 130 cases with a CL were administered prostaglandin F2α, followed 48 h later with a second injection of buserelin (8-10 μg). Fixed-AI was performed 16-20 hours after the last injection. Results: The pregnancy rate was 51.5 % (67/130). The pregnancy rate after a short interval (50-70 d) from calving to entering the program was significantly higher than that after a long interval (>70 d). Conclusion: This protocol seems to give acceptable pregnancy results in beef herds and its effect on saving labour is notable

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2–6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors

Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p &lt; 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections