Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

Mineral density volume gradients in normal and diseased human tissues.

Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

Oral application of bacterial lysate in infancy diminishes the prevalence of atopic dermatitis in children at risk for atopy.

Numerous interventions such as avoidance of food allergens, prolonged breast feeding and supplementation of pro-and/or prebiotics have been tried as primary prevention of atopic dermatitis. Recent data suggest that prevention of infantile eczema is possible in a subgroup of children by feeding bacterial lysates early in life. Bacterial lysates of Escherichia coli and Enterococcus faecalis were found to impair allergic immune responses in rats. An interventional trial in 606 infants at risk for atopy showed a reduction of atopic dermatitis at the end of the treatment phase (month 2 until month 7) of 50% in a subgroup of children with single heredity for atopy. This was even more pronounced in the group of children with paternal heredity for atopy. This effect was still seen at age 1 year. There was no effect on food sensitisation. In conclusion, an immune modulation in terms of prevention of atopic dermatitis in infancy if single atopic family history is present seems to be possible by feeding bacterial lysates early in life.

Seven quassinoids from Fructus Bruceae with cytotoxic effects on pancreatic adenocarcinoma cell lines.

Our previous studies showed that the alcohol extract of the fruit of Brucea javanica (Fructus Bruceae) possessed significant cytotoxicity in pancreatic adenocarcinoma cell lines. A bioassay-guided fractionation and purification resulted in the isolation and characterization of seven quassinoids including brusatol, bruceine D, bruceine H, yadanzioside A, yadanzioside G, javanicoside C and bruceantinoside A. Among them, brusatol exhibited the most potent in vitro antipancreatic cancer action, with IC(50) values of 0.36 µm and 0.10 µm on PANC-1 and SW1990 cell lines, respectively. This is the first report on the antipancreatic adenocarcinoma activity of brusatol.

The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.

BACKGROUND: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy. PATIENTS AND METHODS: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells. RESULTS: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group. CONCLUSIONS: TCM did not improve QOL but did have some effects in terms of maintaining immune function.

Ultraviolet electroluminescence from randomly assembled n-SnO(2) nanowiresp-GaN:Mg heterojunction.

Electroluminescence characteristics of a heterojunction light-emitting diode, which was fabricated by depositing a layer of randomly assembled n-SnO(2) nanowires on p-GaN:Mg/sapphire substrate via vapor transport method, were investigated at room temperature. Peak wavelength emission at around 388 nm was observed for the diode under forward bias. This is mainly related to the radiative recombination of weakly bounded excitons at the shallow-trapped states of SnO(2) nanowires, Under reverse bias, near bandedge emission from the p-GaN:Mg/sapphire leads to the observation of emission peak at around 370 nm.

Nonlinear interactions of high-frequency oscillations in the human somatosensory system.

OBJECTIVE: The source of somatosensory evoked high-frequency activity at about 600 Hz is still not completely clear. Hence, we aimed to study the influence of double stimulation on the human somatosensory system by analyzing both the low-frequency activity and the high-frequency oscillations (HFOs) at about 600 Hz. METHODS: We used median nerve stimulation at seven interstimuli intervals (ISIs) with a high time resolution between 2.4 and 4.8 ms to investigate the N15, N20 and superimposed HFOs. Simultaneously, the electroencephalogram and the magnetoencephalogram of 12 healthy participants were recorded. Subsequently, the source analysis of precortical and cortical dipoles was performed. RESULTS: The difference computations of precortical dipole activation curves showed in both the low- and high-frequency range a correlation between the ISI and the latency of the second stimulus response. The cortical low-frequency response showed a similar behavior. Contrarily, in the second response of cortical HFOs this latency shift could not be confirmed. We found amplitude fluctuations that were dependent on the ISI in the low-frequency activity and the HFOs. These nonlinear interactions occurred at ISIs, which differ by one full HFO period (1.6 ms). CONCLUSIONS: Low-frequency activity and HFOs originate from different generators. Precortical and cortical HFOs are independently generated. The amplitude fluctuations dependent on ISI indicate nonlinear interference between successive stimuli. SIGNIFICANCE: Information processing in human somatosensory system includes nonlinearity.

Primary versus secondary immunoglobulin E sensitization to soy and wheat in the Multi-Centre Allergy Study cohort.

BACKGROUND: IgE sensitization to soy and wheat is classified as 'primary' when generated by food ingestion and 'secondary' when it as a consequence of primary sensitization to cross-reacting pollen antigens via inhalation. The age-specific relevance of these categories of sensitization throughout childhood is unknown. OBJECTIVE: To monitor the natural course of IgE sensitization against common food allergens in childhood in relation to sensitization against cross-reactive airborne allergens. METHODS: The German Multi-Centre Allergy Study with follow-up from birth to age 13 recruited initially 1314 children. IgE antibody levels against cow's milk, hen's egg, soy, wheat, mites, cat and dog dander, birch and grass pollens were tested. Longitudinal data were analysed from the 273 children with sera obtained at age 2, 5, 7 and 10 years of age. RESULTS: The point prevalence of sensitization (>1.0 kU/L) to milk and egg allergens progressively decreased from about 4% at 2 years to <1% at 10 years. By contrast, the prevalence of IgE to wheat and soy progressively increased with age, from 2% to 7% (soy) and from 2% to 9% (wheat). At 10 years of age, IgE to grass pollen was detected in 97% and 98% of the children reacting against soy and wheat, respectively; IgE to birch pollen was observed in 86% and 82% of the children reacting against soy and wheat, respectively. Early IgE sensitization to soy or wheat preceded that to grass or birch pollen in only 4% and 8% of participants sensitized to soy and wheat, respectively. CONCLUSION: IgE sensitization to soy and wheat is relatively uncommon and mostly primary in early infancy, more frequent and mostly secondary to pollen sensitization at school age. Clinical Implications Awareness should be raised to avoid unnecessary diet restrictions due to the high frequency of clinically irrelevant, secondary sensitization to soy and wheat in schoolchildren with pollinosis.

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Staphylococcus aureus subcutaneous abscess complicating acupuncture: need for implementation of proper infection control guidelines.

We report a case of Staphylococcus aureus subcutaneous abscess centered over the Jizhong acupuncture point (DU 6) which lies along the Du (Back midline) meridian after acupuncture at the corresponding acupuncture point for low back pain. The patient recovered after surgical debridement and drainage and 5 weeks of cloxacillin therapy. Among the 16 anecdotal case reports of pyogenic bacterial infections complicating acupuncture described in the English literature (MEDLINE Search 1996-2002), S. aureus was documented to be the causative agent in 9 (56%). Three patients had septic arthritis, 2 had chronic osteomyelitis, 2 had abscess formation, 1 had chondritis, and 1 had infective endocarditis. Five patients had S. aureus bacteremia. All patients who recovered required prolonged antibiotic treatment of 5-6 weeks, and 6 required drainage and/or debridement. Overall, 3 patients (30%) died. S. aureus causes significant morbidity and mortality in patients who receive acupuncture treatment. More resources should be spent on implementation of proper infection control guidelines, as the money lost due to prolonged hospitalization and medication would far exceed that used for implementation.

Biological and chemical factors influencing shallow lake eutrophication: a long-term study.

The focus of eutrophication research has tended to be upon short-term and experimental studies. However, given the range of factors that can influence eutrophication dynamics, and that these matter over a range of time scales, some discrete, some continuous, eutrophication dynamics may only be fully investigated when long-term, time-series data are available. The present study aims to evaluate the interacting effects of abiotic processes and biotic dynamics in explaining variations of phytoplankton biomass in a eutrophic shallow lake, Barton Broad (Norfolk, UK) using a long-term data set. Multivariate statistical analysis shows that the inter-relationships between phytoplankton variability, nutrient and grazing factors were highly sensitive to seasonal periodicity. In spring phytoplankton biomass was related to phosphorus, nitrogen and silicon. In summer phytoplankton biomass was associated with phosphorus, nitrogen and zooplankton. In autumn phytoplankton was related to phosphorus, nitrogen, silicon and zooplankton. In winter, no significant relationship could be established between phytoplankton and environmental variables. This paper improves our understanding of the governing role of nitrogen, phosphorus, silicon and zooplankton upon phytoplankton variability, and hence, improves management methods for eutrophic lakes.

Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes.

Isoflavones have drawn much attention because of their benefits to human health. These compounds, which are produced almost exclusively in legumes, have natural roles in plant defense and root nodulation. Isoflavone synthase catalyzes the first committed step of isoflavone biosynthesis, a branch of the phenylpropanoid pathway. To identify the gene encoding this enzyme, we used a yeast expression assay to screen soybean ESTs encoding cytochrome P450 proteins. We identified two soybean genes encoding isoflavone synthase, and used them to isolate homologous genes from other leguminous species including red clover, white clover, hairy vetch, mung bean, alfalfa, lentil, snow pea, and lupine, as well as from the nonleguminous sugarbeet. We expressed soybean isoflavone synthase in Arabidopsis thaliana, which led to production of the isoflavone genistein in this nonlegume plant. Identification of the isoflavone synthase gene should allow manipulation of the phenylpropanoid pathway for agronomic and nutritional purposes.

Unilateral sacroiliitis as an unusual complication of acupuncture.

Septic sacroiliitis is an uncommon disease and is rarely reported as a complication of acupuncture. We present a case of unilateral septic sarcoiliitis, which developed as a complication of acupuncture because of failure to sterilise the skin properly before treatment. Bone scan and computed tomography were positive for sacroiliitis. After a course of antibiotics with oxacillin for 6 weeks, the condition was completely improved. This case report stresses the importance of sterilisation procedures before acupuncture therapy.

Respiratory syncytial virus infection: its role in aeroallergen sensitization during the first two years of life.

Our aim was to study the influence of infection with the respiratory syncytial virus (RSV) in non-hospitalized infants on sensitization to aeroallergens and the early manifestation of atopy. Six hundred and nine infants from the prospective German Multicenter Cohort Study on Atopy were included, 38% of whom had an elevated atopic risk. RSV IgG and IgM antibodies were tested by ELISA with gradient purified RSV antigen. Specific IgE against mites, cat dandruff, birch and grass pollens and relevant nutritional antigens were tested with CAP-RAST-FEIA (Pharmacia, Sweden). Of the cord sera 99% were positive for RSV-IgG, 44.7% at one year and 64.2% (n = 265) at two years of age. The positivity rate after 12 months varied with the season of birth, the number of siblings and the degree of exposure to tobacco smoke; and correlated closely with attacks of wheezing during infancy. Twenty (2.8%) children were found to be sensitized against at least one aeroallergen at one year, and 28 (10.5%) at two years. By the first birthday, mite sensitization (n = 3) could only be seen in the RSV-infected children; grass pollen sensitization (n = 9) was associated with RSV seropositivity (logistic regression model including the confounders mentioned above: with RSV IgG < p = 0.048 > and IgM < p = 0.0006 >), as was birch sensitization (n = 5) with RSV IgM (p = 0.009). No such differences could be detected at two years. No correlation of RSV seropositivity to any allergic manifestation could be found. We conclude, that it is only in the first year of life, that RSV infection plays a significant role in promoting sensitization against aeroallergens, which do not at this time produce allergic symptoms.

The effect of haloperidol on met-enkephalin, beta-endorphin, cholecystokinin and substance P in the pituitary, the hypothalamus and the striatum of rats during aging.

1. Haloperidol increased the Met-enk level in the striatum at all age groups. However, the Met-enk level was decreased in AL of young and middle-aged rats by the drug. 2. Haloperidol elevated the beta-end level in AL and CCK level in NIL in young rats only. 3. The SP content in NIL was decreased by haloperidol in all age groups. 4. With regard to the effect of aging, Met-enk level in AL of middle-aged rats was higher than that in young rats. The beta-end level in AL also increased in old rats. 5. Aging modified the haloperidol effect on beta-end level in AL and CCK level in NIL as the effect was only observed in young rats. 6. In addition, aging caused a blunted response of Met-enk level to haloperidol in the striatum but an increased response of SP content to haloperidol in the NIL.

Constitutive mucin secretion linked to CFTR expression.

Mucus plugging is a hallmark of cystic fibrosis, but the link between the defective gene product, the cystic fibrosis transmembrane conductance regulator, and the abnormal mucus phenotype is unclear. To demonstrate CFTR involvement in mucin glycoprotein secretion in epithelial cells, a retroviral vector was used to overexpress CFTR in gallbladder epithelial cells, and constitutive mucin labeling and secretion were monitored. Achievement of high-level vector expression was confirmed by transduction with marker genes. Cells transduced with vectors carrying CFTR cDNA showed 5-fold increased expression of CFTR by Western blotting. Mucin labeling and secretion were 4-fold elevated in transduced cells. These results suggest constitutive mucin synthesis and secretion in gallbladder epithelial cells are regulated by CFTR.

IgE-mediated allergic reactions to potatoes.

We investigated sera of 12 patients with IgE-mediated hypersensitivity reactions to potato, using different in vitro methods. Radioallergosorbent test classes 2-4 (7.6-46.5% binding) were measured with potato allergen disks. Immunoblot detected allergen bands with an isoelectric point range of approximately 4.5-5.2 and mainly in a molecular weight range between 16.00 and 30.00 kD. But also at molecular weights of 43.00 and 65.00 kD allergen bands (IgE specificities) could be detected. Histamine release assay performed with isolated fractions of the potato extract showed a great individual variation and positive results of fractions of molecular weights between 10.00 and 80.00 kD. From our data we conclude that raw potato is a 'multiallergenic' vegetable.

Neonatal jaundice: its prevalence in Chinese babies and associating factors.

A prospective study of 1238 full-term Chinese newborn infants was conducted to determine the incidence of neonatal jaundice and associated factors. A significantly more severe degree of hyperbilirubinaemia was present in infants whose ABO blood group was incompatible with that of their mothers and those who were deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Among the remainder, clinical jaundice was present in 87% and 23.9% had a peak serum bilirubin (SB) concentration greater than 204 mumol/l. Factors that were found to have an association with a higher peak SB concentration included: male infants; elder siblings who had a history of neonatal jaundice; and breast-fed infants with or without supplementation with formula feed. Factors that were found to have no significant association with the peak SB concentration were: gestational age; birthweight; the mode of delivery of the infants; maternal consumption of Chinese herbs and syntocinon induction or augmentation of labour.