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Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1–10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti- Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients. [ABSTRACT FROM AUTHOR]

Patients with chronic mucocutaneous candidiasis (CMC) suffer persistent infections with the yeast Candida. CMC includes patients with autoimmune regulator (AIRE) gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, and dendritic cells (DCs), as central orchestrators, may underlie pathogenic disease mechanisms. In 29 patients with CMC (13 with APECED) and controls, we generated monocyte-derived DCs, stimulated them with Candida albicans, Toll-like receptor-2/6 ligand and lipopolysaccharide to assess cytokine production [interleukin (IL)-12p70, IL-23, interferon (IFN)-γ, IL-2, tumour necrosis factor (TNF)-α, IL-6, transforming growth factor-β, IL-10, IL-5, IL-13] and cell-surface maturation marker expression (CD83, CD86, human leucocyte antigen D-related). In both APECED and non-APECED CMC patients, we demonstrate impairment of DC function as evidenced by altered cytokine expression profiles and DC maturation/activation: (1) both groups over-produce IL-2, IFN-γ, TNF-α and IL-13 and demonstrate impaired DC maturation. (2) Only non-APECED patients showed markedly decreased Candida-stimulated production of IL-23 and markedly increased production of IL-6, suggesting impairment of the IL-6/IL-23/T helper type 17 axis. (3) In contrast, only APECED patients showed DC hyperactivation, which may underlie altered T cell responsiveness, autoimmunity and impaired response to Candida. We demonstrate different pathogenic mechanisms on the same immune response pathway underlying increased susceptibility to Candida infection in these patients. [ABSTRACT FROM AUTHOR]

Background Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome (APECED; OMIM 240300) is a rare autosomal recessive disorder defined by a variable combination of endocrine failure, chronic mucocutaneous candidiasis (CMC), and dystrophy of the dental enamel and nails. APECED is caused by mutations in the autoimmune regulator gene ( AIRE). Alopecia areata (AA) and vitiligo are diseases with autoimmune pathogeneses, and have been recognized as part of the APECED complex. There are rare reports of other cutaneous manifestations. Objectives We sought to delineate the dermatological features of APECED in an Irish case series with emphasis on timing of their appearance and association with disease severity. Furthermore, we looked for evidence of genotype: phenotype correlation. Finally, we wanted to determine if the ectodermal changes described represent a primary ectodermal dysplasia or whether the ectodermal manifestations are secondary phenomena. Methods Irish patients with APECED were invited to attend a multidisciplinary clinic (Dermatology, Endocrinology, Dentistry and Ophthalmology) held in Our Lady's Hospital for Sick Children, Dublin. Clinical data were compiled from case notes and questionnaires. All patients had a detailed cutaneous examination. Blood samples were obtained for mutational analysis. Results Eighteen patients (seven males and 11 females) from 15 families were interviewed and examined. The mean age at diagnosis was 6 years (range 8 months–18 years). All patients had evidence of CMC, 13 (72%) had candidal onychomycosis or paronychia, six (33%) had AA and two had vitiligo. In the case of two patients the diagnosis was made on recognition of dermatological manifestations and confirmed by mutational analysis. Both patients developed Addison's disease on follow-up. CMC was an early feature, often predating diagnosis (10 of 18). AA and vitiligo presented later, and may reflect more severe disease in these cases. There was no correlation between the AIRE mutations identified on mutational analysis and the clinical presentation. We found no evidence of an isolated nail dystrophy or features consistent with a primary ectodermal dysplasia. Conclusions APECED is a rare but complex and potentially life-threatening autoimmune disease. CMC is a common and early feature; diagnosis at this stage may pre-empt life-threatening endocrinological crises. It is important for dermatologists to be aware of this association as they are likely to be the earliest clinicians who encounter these children. AA and vitiligo in our series occurred in the setting of established disease. The term ‘ectodermal dystrophy’ is misleading as the ectodermal features described in our series and in the literature are most likely to be secondary phenomena. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that, when smoking habits are comparable, women incur a higher risk of lung cancer than men. Because smokers are also at risk for bladder cancer, we investigated possible sex differences in the susceptibility to bladder cancer among smokers.Methods: A population-based, case--control study was conducted in Los Angeles, CA, involving 1514 case patients with bladder cancer and 1514 individually matched population control subjects. Information on tobacco use was collected through in-person interviews. Peripheral blood was collected from study participants to measure 3- and 4-aminobiphenyl (ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to determine whether the risk of bladder cancer differs between male and female smokers and whether female smokers exhibit higher levels of ABP-hemoglobin adducts than male smokers with comparable smoking habits. All statistical tests were two-sided.Results: Cigarette smokers had a statistically significant 2.5-fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus higher tar cigarettes, or the pattern of inhalation did not modify the risk. The risk of bladder cancer in women who smoked was statistically significantly higher than that in men who smoked comparable numbers of cigarettes (P =.016 for sex-lifetime smoking interaction). Consistent with the sex difference in smoking-related bladder cancer risk, the slopes of the linear regression lines of the 3- and 4-ABP--hemoglobin adducts by cigarettes per day were statistically significantly steeper in women than in men (P values for sex differences <.001 and.006, respectively).Conclusion: The risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. [ABSTRACT FROM AUTHOR]

Issue/problem: Leptospirosis is an endemic disease which is mandatorily notifiable in Spain. It is associated with occupational activities in which workers come into contact with rat urine. In our region, this disease’s rates of prevalence and incidence are highest among red swamp crayfish collectors (Procambarus clarkii) (RSCC). The increase in outbreaks of leptospirosis over the last 7 years has motivated us to design and implement a Clinical Practice Guide (CPG) for health workers, informational material for the general population, and ID cards and specific information aimed at RSCCs, as a means of reducing the incidence rate. The guide may also serve as a useful tool in other regions and countries with activities associated with Leptospira-infected wetlands. Description of the problem: The material we have designed is the result of a research project funded by the Consejería de Salud de Andalucía to identify leptospirosis incidence, prevalence, and risk factors among wetland RSCCs. Hardly any CPGs or informational material exist about this disease. The GPC and the educational material designed may be very useful in other environments with a high risk of leptospirosis. Results: Prevalence of the disease was higher among RSCCs than among the general population (9.8% vs 3.1%) (OR: 3.4; CI 95%: 1.1-12.7) and accumulated incidence was 17.4%. Less than half of the workers adopted appropriate individual preventive measures. Lessons: The risk of contracting leptospirosis is 3.4 times greater for the RSCC population than it is for the general population. Early detection and antibiotic therapy prevent aggravation of the disease in serious cases and may even prevent deaths. Education and the promotion of preventive measures among RSCCs reduces the risk of infection. The training of health professionals and the design of decision algorithms shorten and improve the quality of treatment for leptospirosis patients. Key messages: Early detection and antibiotic therapy reduce the incidence of severe forms of leptospirosis. The material designed will help the risk population to adopt preventive measures and seek medical attention. [ABSTRACT FROM AUTHOR]

The activity of imipenem against nosocomial strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-resistant Staphylococcus aureus resistant to some third-generation cephalosporins, aztreonam, or ciprofloxacin was assessed. These strains represent the most prevalent multi-resistant nosocomial microorganisms in Chile since they were isolated from clinical specimens in 11 Chilean hospitals. A high proportion of the strains were resistant to several beta-lactams, yet all strains of K. pneumoniae and Acinetobacter spp. were susceptible to imipenem; resistance was exhibited by only one strain of P. aeruginosa and 16 strains of S. aureus. Synergy between cefotaxime and clavulanic acid was found in almost all strains of K. pneumoniae, suggesting the presence of plasmid-coded beta-lactamases, probably with extended-spectrum activity. Killing A. baumannii by imipenem was rapid, but slower for P. aeruginosa. Killing of K. pneumoniae was also somewhat slower despite the lower MIC of imipenem for this strain. Bactericidal activity was even slower against one strain of methicillin-resistant S. aureus. These results suggest that imipenem would be an adequate alternative to other broad-spectrum agents in the treatment of infections due to nosocomial multi-resistant Gram-negative bacilli. [ABSTRACT FROM AUTHOR]

This study describes an in vitro model of peripheral blood mononuclear cell (PBMC) migration through human endothelial cells, held on polycarbonate inserts, which allows automatic differential counting of migrated cells as lymphocytes and monocytes. Using this system it was found that treatment of PBMC with the phosphodiesterase (PBMC) inhibitors theophylline (at 1 and 10 μg. ml) and RO-20-1724 (at I μM) inhibited the migration of the lymphocyte component to 64.2 ±16.4%. 48.9 ± 3.0% and 47.5 ± 5.8% of the control values. respectively, while the migration of the monocytes component was largely unaffected. The POE inhibitors needed to be present during the assay to inhibit migration, whereas pie-treatment of either the endothelium or the PBMC did not consistently effect lymphocyte migration. The drugs also inhibited the migration of lymphocytes through control inserts, either uncoated or coated with fibronectin. suggesting that some of the inhibition is an effect on lymphocyte motility rather than lymphocyte endothetial interact ions. Lymphocyte migration through fibronectin-coated filters was significantly enhanced compared with uncoated filters. Activation of the PBMC by anti-CD3 MoAb increased motility and migration by tip to 300%. This migration appeared to be greatly inhibited by the PDE inhibitors, although the effect was complicated by problems of lymphocyte aggregation. This study provides a novel method of measuring mononuclear cell transendothelial migration. and suggests a possible role of PDE inhibitors in reducing this Process. [ABSTRACT FROM AUTHOR]

The article presents a case study of a five-year-old girl with itchy papular eruption and blisters on her legs extending to other parts of her body including the arms, trunk and palms. It mentions that the patient was suffering from atopic dermatitis and irritation to egg, peach and plum. It also notes her diagnosis with lichen planus pemphigoides (LPP) which is considered an autoimmune blistering disease known for its inducement of vesiculobullous skin wounds.

The susceptibility of 49 strains of Aeromonas hydrophila and 77 strains of Enterobacteriaceae towards nalidixic acid was compared by tube dilution and agar diffusion methods. A higher susceptibility was exhibited by Aerom. hydrophila and no overlap in MICs was found for strains of the two groups of microorganisms. Discs containing 0.25 microgram of nalidixic acid produced measurable zones of growth inhibition with Aerom. hydrophila and no zones with the Enterobacteriaceae. The use of a disc with 0.25 microgram of nalidixic acid for the primary differentiation of strains of Aerom. hydrophila from those of the Enterobacteriaceae with similar biochemical properties is suggested. [ABSTRACT FROM AUTHOR]