Hand strength and dexterity in individuals with hand eczema.

BACKGROUND: Patients with hand eczema often describe symptoms such as pain, clumsiness and difficulty flexing their fingers, thus impairing the function of the hand. OBJECTIVE: The aim of this study was to investigate whether hand eczema is associated with a measurable impairment of hand strength and dexterity. We also studied the relationship between hand function and the ability to perform activities of daily living (ADL), pain level and quality of life measured with the Dermatology Life Quality Index (DLQI). METHODS: Twenty-one participants with ongoing hand eczema were examined with well-established methods for measuring hand grip strength, pinch strength and dexterity. A questionnaire was designed to investigate perceived ability to perform ADL. The participants were also asked to grade their current pain level, and the DLQI was used to assess the participants' quality of life. A group of 12 participants was reinvestigated when healed. RESULTS: The participants demonstrated a significant improvement in all functional tests when healed. There was a strong correlation between ADL and both dexterity and hand grip strength. There was also a strong correlation between ADL and pain. All participants reported some difficulty performing ADL. CONCLUSIONS: Our results suggest that ongoing hand eczema may lead to a measurable decrease of strength and dexterity of the hand, leading to an impairment of the ability to perform ADL and consequently to a poorer quality of life.

Wet work exposure and hand eczema among healthcare workers: a cross-sectional study.

BACKGROUND: Hand eczema is more common in healthcare workers than in the general population. Hands are subject to changing occupational exposures as a result of mandatory hygiene regulations for healthcare workers. OBJECTIVES: To describe exposure to hygiene procedures and investigate the associations between occupational hand washing, use of nonsterile gloves and hand disinfectant, and self-reported hand eczema. METHODS: This was a cross-sectional study; an electronic questionnaire was distributed to 28 762 hospital employees in southern Sweden. Nurses, assistant nurses or physicians constituted the group of healthcare workers analysed. Adjustments were made for sex, age, wet work at home, lifestyle factors and atopic dermatitis. RESULTS: In total, 12 288 (43%) responded, including 9051 healthcare workers. In this group the 1-year prevalence of self-reported hand eczema was 21%. On a daily basis, 30% reported hand washing with soap > 20 times at work, 45% used hand disinfectants > 50 times and 54% wore nonsterile gloves for > 2 h. After adjustment for confounding factors, a dose-dependent association with self-reported hand eczema was found for the daily number of hand washes with soap at work and time working with disposable gloves but not for alcoholic disinfectant use. Hand washing outside work was not associated with self-reported hand eczema in the adjusted multivariate analysis. CONCLUSIONS: In this study, we found a higher 1-year prevalence of self-reported hand eczema among Swedish healthcare workers than reported in the general population. Hand washing with soap and use of disposable gloves were associated with the occurrence of self-reported hand eczema in a dose-dependent way. Use of hand disinfectant was not associated with self-reported hand eczema.

Skincare products containing low concentrations of formaldehyde detected by the chromotropic acid method cannot be safely used in formaldehyde-allergic patients.

BACKGROUND: Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in skincare products. It has been found that formaldehyde at concentrations allowed by the European Cosmetics Directive can cause allergic contact dermatitis. However, we still lack information on whether formaldehyde at low concentrations affects dermatitis in formaldehyde-allergic individuals. OBJECTIVES: To study the effects of low concentrations of formaldehyde on irritant contact dermatitis in formaldehyde-allergic individuals. METHODS: Fifteen formaldehyde-allergic individuals and a control group of 12 individuals without contact allergy to formaldehyde and formaldehyde releasers were included in the study. The individuals performed the repeated open application test (ROAT) during 4 weeks with four different moisturizers releasing formaldehyde in concentrations that had been determined as > 40, 20-40, 2·5-10 and 0 p.p.m. by the chromotropic acid (CA) spot test. Dimethyloldimethylhydantoin was used as a formaldehyde releaser in the moisturizers. The ROAT was performed on areas of experimentally induced sodium lauryl sulfate dermatitis. The study was double blind, controlled and randomized. RESULTS: Nine of the 15 formaldehyde-allergic individuals had reappearance or worsening of dermatitis on the areas that were treated with moisturizers containing formaldehyde. No such reactions were observed in the control group (P < 0·001) or for the moisturizers without formaldehyde in the formaldehyde-allergic individuals (P < 0·001). CONCLUSIONS: Our results demonstrate that the low concentrations of formaldehyde often found in skincare products by the CA method are sufficient to worsen an existing dermatitis in formaldehyde-allergic individuals.

Clinically relevant contact allergy to formaldehyde may be missed by testing with formaldehyde 1·0%.

BACKGROUND: It has been found that patch testing with 15 µL formaldehyde 2·0% aq. detects twice as many allergies as by testing with 1·0%. The clinical relevance of positive patch test reactions is often difficult to determine. Repeated open application tests are simple to do and help to evaluate the significance of patch test results. OBJECTIVES: To study the clinical relevance of contact allergy to formaldehyde detected by 2·0% formaldehyde (0·60 mg cm(-2) ) but not by 1·0%. METHODS: Eighteen patients positive to formaldehyde 2·0% but negative to 1·0%, and a control group of 19 patients with dermatitis but without allergy to parabens, formaldehyde and formaldehyde releasers were included in the study. Formaldehyde 2000 p.p.m., the maximum concentration permitted in leave-on cosmetics according to the EU Cosmetics Directive, was added to a batch of moisturizer preserved with parabens. The same batch without formaldehyde served as a control. The study was double-blinded and randomized. The patients were provided with both moisturizers and instructed to apply one of them twice a day on a marked-out 5 × 5-cm area on the inside of one upper arm and the other moisturizer on the other arm. Reading of the test sites was done once a week for a maximum of 4 weeks. RESULTS: In the control group there were no allergic reactions to either of the moisturizers. Nine of 17 formaldehyde-allergic patients reacted with an allergic reaction to the moisturizer which contained formaldehyde (P < 0·001). No positive reactions were observed to the moisturizer without formaldehyde. CONCLUSIONS: Our results demonstrate that contact allergy to formaldehyde 2·0% may be clinically relevant.

Risk of contact allergy and dermatitis at a wind turbine plant using epoxy resin-based plastics.

AIMS: To identify workplace and individual risk factors for occupational contact allergy and dermatitis. METHODS: A cross-sectional study was carried out at an international company producing wind turbine systems in Denmark. A cohort of 724 production workers at four facilities was highly exposed to epoxy resin as well as other chemicals. A screening questionnaire (participation rate 84.7%) was followed by an interview by an occupational physician and a dermatological examination, including patch testing, for a comprehensive list of potential workplace sensitizers. RESULTS: Clinically diagnosed dermatitis was found among 214 workers (35.8%) and contact allergy to materials used in the workplace was found in 66 workers (10.9% of the total population and 20.3% of those who underwent patch testing). Of the 66 workers with a work-related allergy, 40 (60.6%) were allergic to epoxy compounds, 25 (37.9%) to hardeners and ten (15.2%) to other workplace materials, where one person showed an allergy only to these materials. Experiencing contact allergy was related to older age and longer employment in the workplace-however, neither of these risk factors was significant. The main risk factor for current dermatitis was contact allergy to materials used in the workplace, determined by patch testing, OR=5.4 (95% CI 3.9-9.9). Fewer days of absence from work was also related to current dermatitis, OR=2.0 (95% CI 1.2-3.5). CONCLUSIONS: In a cohort of workers with extensive exposure to chemicals related to epoxy-resin systems, contact dermatitis and allergy was prevalent. Older age and longer duration of employment at the workplace were individual risk factors for allergy to workplace materials, whilst work-related allergies and longer duration of employment at the workplace were significant risk factors for current dermatitis.

Epoxy-based production of wind turbine rotor blades: occupational dermatoses.

Occupational dermatoses were investigated in a factory producing rotor blades for wind turbines by an epoxy-based process. In a blinded study design, 603 workers were first interviewed and thereafter clinically examined. Based on a history of work-related skin disease, clinical findings of dermatitis, or both, 325 (53.9%) of the workers were patch tested with a specially profiled occupational patch-test series and the European standard patch-test series. Calculated on all investigated workers, 17.1% of the workers were diagnosed with occupational dermatoses caused by work. Occupational allergic contact dermatitis was found in 10.9% of the workers. The estimated frequency of irritant contact dermatitis caused by work was 6.1%. Dermatitis on the hands was associated with contact allergy to epoxy resin (P = 0.017). The number of days on leave before the clinical examination was negatively associated with the presence of dermatitis (P = 0.001). Among workers employed 7-12 months, the frequency of occupational contact allergy was higher than that among workers employed for

Chemical analysis of monomers in epoxy resins based on bisphenols F and A.

Diglycidyl ether of bisphenol A (DGEBA) is the monomer and most important contact allergen in epoxy resin(s) based on bisphenol A (DGEBA-R). Both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) methods are available for the analysis of products containing DGEBA-R. With respect to detection and quantification, epoxy resins of the bisphenol F-type, i.e. epoxy resins containing the isomers of diglycidyl ethers of bisphenol F (DGEBF), are not as well investigated as DGEBA-R. The isomers of DGEBF are p,p'-DGEBF, o,p'-DGEBF and o,o'-DGEBF. Both p,p'-DGEBF and o,p'-DGEBF have been shown to be contact allergens in humans, and all 3 isomers are sensitizers in the guinea pig maximization test. We aimed (i). to develop HPLC methods for separation and purification of the individual DGEBF isomers, (ii). to detect and quantify the DGEBF isomers in epoxy resins of the bisphenol F-type and (iii). to evaluate and develop the TLC as a method for the detection of the DGEBF monomers. We found the total content of the DGEBF isomers in the investigated epoxy resins of the bisphenol F-type to vary from 17.0 to 81.7% w/w. Some of them also contained 0.1-2.4% w/w DGEBA. The HPLC method showed a sensitivity that was 2000-20 000x higher than that obtained with the TLC method for the DGEBF monomers. We concluded that the range of the DGEBF isomer content in epoxy resins of the bisphenol F-type is approximately the same as the monomer content in liquid compared to solid DGEBA-R. The relevance of contact allergy to DGEBA-R can remain unrecognized if the suspected product is an epoxy resin of the bisphenol F-type, which is analysed with the TLC method.

Occupational dermatoses in a metalworking plant.

In a plant producing advanced components for engines and drivelines we undertook a survey of occupational dermatoses, based on a questionnaire, clinical examination, and patch testing with a standard series and a series of samples from the working environment. The questionnaire was given to all 430 employees and it was answered and returned by 382 of these. 214 reported having had or having skin manifestations during the time of employment suspected of being work-related. 183 employees (164 metal workers, 19 office staff) participated in the clinical investigation, 182 (163 metal workers, 19 office staff) being patch tested. Occupational dermatoses were diagnosed in 23 of these 163 (14.1%) and in 1 of these 19 (5.3%). In all, irritant contact dermatitis was diagnosed in 12 metal workers, occupational allergic contact dermatitis in 11 (10 metal workers and 1 office clerk) and folliculitis in 1 metal worker. In the 11, neat oils were the cause in 4 workers, a water-based cutting fluid in 3 and various biocides in 4.

Sensitizing capacity and cross-reaction pattern of the isomers of diglycidyl ether of bisphenol F in the guinea pig.

In this study, the sensitizing capacities of the 3 main low-molecular-weight isomers of epoxy resins based on diglycidyl ether of biphenol F (DGEBF) were investigated in a guinea pig maximization test (GPMT). The isomers are p,p'-DGEBF, o,p'-DGEBF, and o,o'-DGEBF. The sensitization capacities were compared to diglycidyl ether of bisphenol A (DGEBA), which is the main constituent in the most common epoxy resin. The cross-reaction pattern between all 4 compounds was also investigated. It was found that all 3 DGEBF isomers were potent sensitizers. It was also found that p,p'-DGEBF, o,p'-DGEBF, and DGEBA cross-reacted with one another, and that animals induced with o,o'-DGEBF reacted significantly only to o,p'-DGEBF, but not to the other 2 DGEBF isomers or DGEBA.

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.

Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions.

Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

Constitutive expression of interferon-induced human MxA protein in transgenic tobacco plants does not confer resistance to a variety of RNA viruses.

MxA is a key component in the interferon-induced antiviral defense in humans. After viral infections, MxA is rapidly induced and accumulates in the cytoplasm. The multiplication of many RNA viruses, including all bunyaviruses tested so far, is inhibited by MxA. These findings prompted us to express MxA in plants in an attempt to create resistance to tospoviruses. Here, we report the generation of transgenic tobacco plants that constitutively express MxA under the control of the 35 S cauliflower mosaic virus promotor. Northern and western blot analysis confirmed the expression of MxA in several transgenic plant lines. MxA expression had no obvious detrimental effects on plant growth and fertility. However, challenge experiments with tomato spotted wilt virus, tomato chlorotic spot virus, and groundnut ringspot virus revealed no increased resistance of MxA-transgenic tobacco plants to tospovirus infections. Neither was the multiplication of tobacco mosaic virus, cucumber mosaic virus and potato virus Y inhibited in MxA-transgenic plants. The results indicate that the expression of human MxA alone does not enhance virus resistance in planta.

Dominant-negative mutants of human MxA protein: domains in the carboxy-terminal moiety are important for oligomerization and antiviral activity.

Human MxA protein is an interferon-induced 76-kDa GTPase that exhibits antiviral activity against several RNA viruses. Wild-type MxA accumulates in the cytoplasm of cells. TMxA, a modified form of wild-type MxA carrying a foreign nuclear localization signal, accumulates in the cell nucleus. Here we show that MxA protein is translocated into the nucleus together with TMxA when both proteins are expressed simultaneously in the same cell, demonstrating that MxA molecules form tight complexes in living cells. To define domains important for MxA-MxA interaction and antiviral function in vivo, we expressed mutant forms of MxA together with wild-type MxA or TMxA in appropriate cells and analyzed subcellular localization and interfering effects. An MxA deletion mutant, MxA(359-572), formed heterooligomers with TMxA and was translocated to the nucleus, indicating that the region between amino acid positions 359 and 572 contains an interaction domain which is critical for oligomerization of MxA proteins. Mutant T103A with threonine at position 103 replaced by alanine had lost both GTPase and antiviral activities. T103A exhibited a dominant-interfering effect on the antiviral activity of wild-type MxA rendering MxA-expressing cells susceptible to infection with influenza A virus, Thogoto virus, and vesicular stomatitis virus. To determine which sequences are critical for the dominant-negative effect of T103A, we expressed truncated forms of T103A together with wild-type protein. A C-terminal deletion mutant lacking the last 90 amino acids had lost interfering capacity, indicating that an intact C terminus was required. Surprisingly, a truncated version of MxA representing only the C-terminal half of the molecule exerted also a dominant-negative effect on wild-type function, demonstrating that sequences in the C-terminal moiety of MxA are necessary and sufficient for interference. However, all MxA mutants formed hetero-oligomers with TMxA and were translocated to the nucleus, indicating that physical interaction alone is not sufficient for disturbing wild-type function. We propose that dominant-negative mutants directly influence wild-type activity within hetero-oligomers or else compete with wild-type MxA for a cellular or viral target.