Association between HLA-C*04 and American cutaneous leishmaniasis in endemic region of southern Brazil.

Leishmaniasis is a parasitic infectious disease with global repercussions. American cutaneous leishmaniasis (ACL) is endemic in southern Brazil and its pathogenesis varies according to parasite species, immune response, and host genetics. In terms of immunogenetics, many host genes, including HLA (human leukocyte antigen), could be involved in susceptibility to and protection against ACL. Accordingly, the aim of this study was to investigate the association between HLA class I genes (HLA-A, -B, and -C) and ACL in an endemic region of southern Brazil. The allele frequencies of 186 patients diagnosed with ACL and 278 healthy individuals were compared. HLA class I (HLA-A, -B, and -C) typing was carried out by PCR-SSO using Luminex technology. The results revealed an association between the HLA-C*04 allele and the patient study group, in which it appeared more frequently than in the control group [21.5 vs 13.49% (P = 0.0016 and Pc = 0.0258; OR = 1.7560; 95%CI = 1.2227-2.5240)], thereby suggesting an increased susceptibility to ACL. Additional allelic groups such as HLA-A*02, HLA-B*35, HLA-B*45, HLA-C*01, and HLA-C*15 were also implicated; however, further investigation is necessary to confirm their association with ACL. Therefore, the results obtained in this study demonstrate the involvement of HLA class I genes in the susceptibility or resistance to ACL, with significant association between HLA-C*04 and ACL susceptibility.

[Differential diagnosis and management of balanitis]. / Differenzialdiagnose und Management der Balanitis.

Balanitis is a descriptive diagnosis for a heterogeneous group of infectious or inflammatory dermatoses which have to be differentiated from malignant conditions. Balanitis is caused not only by Candida spp. and bacterial infections, including anaerobic bacteria: viral infections, parasites and other sexually transmitted infections (STI) also have to be considered. Lichen planus, psoriasis and contact dermatitis can characteristically lead to inflammatory conditions of the glans penis. In addition to a complete skin examination, a thorough patient history with respect to topically applied products and sexual behavior is essential. Infections must be treated and the glans penis should be kept dry. It is important to ensure a balanced genital hygiene in patients. As a last resort therapeutic circumcision can be considered for most forms of chronic balanitis.

Hypertension is associated with serologically active disease in patients with systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative stress.

OBJECTIVES: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension. METHOD: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806-8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.

Rare human skin infection with Corynebacterium ulcerans: transmission by a domestic cat.

Corynebacterium ulcerans is mainly known for its ability to cause animal infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans. Human cutaneous C. ulcerans infection is a very rare disease that mimics classical cutaneous diphtheria. We present a very rare case of a C. ulcerans skin infection caused by a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3 weeks of therapy with amoxicillin-clavulanate. A pet cat was the probable source of infection. The presence of C. ulcerans in the mouth of the cat was confirmed by 16S rRNA gene analysis and the API Coryne system. In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production. If toxigenicity is present, diphtheria antitoxin should be administered immediately. Carriers and potential infectious sources of C. ulcerans include not only domestic livestock but also pet animals. For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended.

Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin.

The aim of this study was to evaluate different urea-containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short-term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2-10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro-Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin's natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea-containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea-containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.

Evaluation of a particle gel immunoassay as a screening test for syphilis.

BACKGROUND: Recent trends in Western Europe show an increase in sexually transmitted infections. Surveillance data in Switzerland confirm this rising trend. Notifications of syphilis cases nearly doubled in the year 2002 and almost tripled in 2003. This trend necessitates an early correct diagnosis making reliable screening tests mandatory. MATERIALS AND METHODS: In the presented study a particle gel immunoassay (ID-PaGIA syphilis antibody test, Diamed) using recombinant treponemal antigens TpN15, TpN17 and TpN47 was evaluated as a screening test in comparison to the currently used Treponema pallidum particle agglutination test (Serodia-TPPA, Fujirebio). Serum samples were obtained from a cross-sectional sero-epidemiological study among men who have sex with men. Samples were tested with the PaGia and the TPPA. In the case of equivocal results a titrated TPPA of an external laboratory was used as a confirmation test. RESULTS: In total 650 serum samples (48 seropositive patients, 602 negative) were evaluated. The PaGIA showed a sensitivity of 0.89 (43/48) and the TPPA of 0.83 (40/48). This difference was not statistically relevant (p = 0.4). The particle gel assay showed a significantly higher specificity (1.0) compared to the TPPA (0.98) (p = 0.004). CONCLUSION: The PaGIA showed a sensitivity comparable to that of other treponemal tests with an even better specificity. Advantages of the PaGIA are the fast reaction time of only 20 min and the simplicity of the procedure with minimal technical equipment.

[Conventional and molecular diagnosis of cutaneous mycoses]. / Konventionelle und molekulare Diagnostik bei Dermatomykosen.

The clinical presentation of fungal infections of the skin, hair, and nails is varied and sometimes presents a confusing clinical picture. The main objective is to rapidly institute diagnostic measures to avoid delays in therapy with potential expansion of the infection. A variety of laboratory tests are required. Classical methods are based on microscopy, different culture procedures, and histologic examination. Genotypic approaches to detection and identification of fungal pathogens have become very rapid and sensitive, making them additional options for routine diagnosis.

[Working hours and job satisfaction among physicians in hospitals and general practice in Munich. Results of an anonymous questionnaire]. / Arbeitszeit und Arbeitszufriedenheit angestellter und beamteter Arzte in München. Ergebnisse einer anonymen Befragung.

PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis- und Bezirksverband München) performed a survey among employed physicians in Munich on working hours and working conditions. The aim of the study was to assess the extent to which the German law on working hours is actually implemented in employed physicians, and to obtain information about their work satisfaction. METHODS: A questionnaire was sent to all employed physicians in hospitals and medical practices. Participants were asked to give anonymous information and send it back per mail. RESULTS: In total, 2450 out of 5461 physicians took part in the survey. 45% reported that their working hours do not meet the German law on working hours of 1994. 44.4% stated that overtime is not fully recognized by their employers. 43.5% think the job would become more attractive if the law was implemented. 63.3% expect an income loss with the implementation. 53.7% are thinking about quitting their job. For 59.9% the burden of long working hours is an important reason for this. Women are more likely to be given a limited employment contract than men, and their overtime is more rarely recognized in full. CONCLUSION: Many employed physicians in Munich are dissatisfied with their job. The high burden of long working hours is a main reason for this.

The association of the HLA in patients with schizophrenia, schizoaffective disorder, and in their biological relatives.

To determine the association of the HLA in 50 patients with schizophrenia, schizoaffective disorder, 48 healthy controls, 41 biological relatives without psychiatric disease, and 48 biological relatives with mood disorder, the HLA genotype at the class I and class II were determined. The subjects were interviewed by structured diagnostic criteria categorized according to DSM-IV, axis I, (SCID-IV). Significant positive association was found with HLA-B.15 in patients, family with humor disorder and without mental disorder (p=0.003) and negative association of the HLA-B.35 in relatives without psychiatric disease (p=0.03). The HLA-B.15 frequency was significantly increased in a subgroup of patients with age at onset in the early 20s, lower educational achievement, occupational disability, chronically ill, more paranoid type. These findings suggest the existence of some involvement of an immunogenetic mechanism in a subgroup of schizophrenic, schizoaffective patients, and biological relatives.

A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production.

Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.

Specific sHLA in healthy donors and donor-specific sHLA in renal transplant patients.

We studied cadaver kidney transplant recipients to determine if their serum levels of donor-specific class I sHLA correlated with graft outcome. Testing of sHLA was performed by an ELISA sandwich assay using allospecific monoclonal trapping antibodies and anti-beta2-mu detecting antibody. Sufficient sHLA sensitivity (<1 ng/ml) was achieved by using two synergistic trapping antibodies. Suitable antibodies were available for A2 and B7, and data were collected for these two antigens. Stability of these sHLA was determined in plasma and serum as were ranges of normal and background levels. Background levels varied substantially. Five A2- recipients of A2+ grafts and 5 B7- recipients of B7+ grafts were studied with appropriate sHLA levels measured pre-transplant and at intervals post-transplant. Graft outcome was assessed by serum creatinines, renal biopsies and/or therapy for rejection. In the 5 patients (3 A2- and 2 B7-) whose post-transplant donor-specific sHLA never exceeded immunological complications (e.g., post-operative ATN, ureteral obstruction) did not affect the correlation. In the 5 patients with post-transplant levels exceeding pre-transplant levels, subsequent evidence of rejection was observed. Periodic measurement of donor-specific sHLA should be a useful instrument for monitoring renal allograft rejection.

Sperm quality of healthy smokers, ex-smokers, and never-smokers.

The possible effects of cigarette smoking on sperm quality were investigated in a blind study of 333 healthy male volunteers 19 to 40 years of age. All subjects with clinically proven abnormalities, operations, or inflammatory diseases of the genital organs, exposure to radiation exceeding routine x-ray examination, or medication were excluded, and the data from 150 smokers, 37 ex-smokers, and 52 never-smokers were evaluated. There was a small but insignificant decrease in sperm density from never-smokers to ex-smokers and to smokers. Eight smokers (6%) had sperm counts less than 1 X 10(6)/ml, whereas none of the ex-smokers or never-smokers fell into this category. This difference, however, is not statistically significant (P = 0.084). No statistically significant effect of smoking habits on sperm density, motility, and morphologic features was detected. It is concluded that smoking does not affect the motility and morphologic features of sperm in healthy adult men. The diminished sperm density in heavy smokers may be related to factors associated with smoking.

Dosimetry of Gamma Knife and linac-based radiosurgery using radiochromic and diode detectors.

In stereotactic radiosurgery the choice of appropriate detectors, whether for absolute or relative dosimetry, is very important due to the steep dose gradient and the incomplete lateral electronic equilibrium. For both linac-based and Leksell Gamma Knife radiosurgery units, we tested the use of calibrated radiochromic film to measure absolute doses and relative dose distributions. In addition a small diode was used to estimate the relative output factors. The data obtained using radiochromic and diode detectors were compared with measurements performed with other conventional methods of dosimetry, with calculated values by treatment planning systems and with data prestored in the treatment planning system supplied by the Leksell Gamma Knife (LGK) vendor. Two stereotactic radiosurgery techniques were considered: Leksell Gamma Knife (using gamma-rays from 60Co) and linac-based radiosurgery (LR) (6 MV x-rays). Different detectors were used for both relative and absolute dosimetry: relative output factors (OFs) were estimated by using radiochromic and radiographic films and a small diode; relative dose distributions in the axial and coronal planes of a spherical polystyrene phantom were measured using radiochromic film and calculated by two different treatment planning systems (TPSs). The absolute dose at the sphere centre was measured by radiochromic film and a small ionization chamber. An accurate selection of radiochromic film was made: samples of unexposed film showing a percentage standard deviation of less than 3% were used for relative dose profiles, and for absolute dose and OF evaluations this value was reduced to 1.5%. Moreover a proper calibration curve was made for each set of measurements. With regard to absolute doses, the results obtained with the ionization chamber are in good correlation with radiochromic film-generated data, for both LGK and LR, showing a dose difference of less than 1%. The output factor evaluations, performed using different methods, are in good agreement with a maximum difference of 1.5% for all field sizes considered (LGK and LR) except the 4 mm helmet used in the LGK unit. In this case, differences exist between diode and radiochromic film measurements and both detectors show data values larger than the prestored OF value of 0.80. Dose profiles measured by radiochromic film and calculated are in excellent agreement for both LGK and LR with a maximum deviation of less than 1.0 mm, when full widths of the dose profiles at 20%, 50%, 80% levels are considered. When external photon beams are used in stereotactic radiosurgery, the 'well selected' radiochromic films are very accurate detectors both for relative and absolute dosimetry. The experimental results, obtained using both radiochromic and diode detectors, show that the 4 mm helmet relative output factor could be underestimated.

Food intake of patients with atopic dermatitis.

There is only restricted information about the nutritional behavior of adult patients with atopic dermatitis (AD). Our purpose was to evaluate the food intake in a series of patients with AD with particular consideration of self-reported food intolerance. Particular attention was paid to the risks of nutrient deficiencies. We examined the intake of 28 food items in 116 AD patients with a food-frequency questionnaire (FFQ). For each food item the cohort was divided in two groups according to whether symptoms were reported or not (symptomatic vs. asymptomatic). We found in a series of food items a significant lower food intake among symptomatic patients. Significantly lower intakes were reported by symptomatic patients for dairy products, fish, egg, pork, oranges, non-specified fruits, apples, kiwis, green or red peppers, peanuts and hazelnuts. We concluded that in symptomatic AD patients supplementation with specific nutrients might become mandatory. This is particularly pertinent for calcium, iodine, vitamin C and n-3 fatty acids.

Tumor necrosis factor beta (TNF-ß) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1.

This study evaluated the association of tumor necrosis factor beta (TNF-ß) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-ß genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-ß NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.