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Biomedical subjects

J Ring

Publications and source records attributed to J Ring.

At least 19 recordsLinked to original sources
PubMed2006

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Adult↗
PubMed2006

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.

Adult↗
PubMed2006

[Allergy--triggers of life-threatening and fatal anaphylaxis].

Cases of life-threatening and fatal anaphylaxis represent the most extreme forms of acute allergic reactions. They are estimated to have an incidence of 1-3 per 10,000 persons, with an associated death rate of 0.5-2%. Medicinal drugs, insect stings and foods are the most common triggering agents. In particular in the case of drugs, the median time lapse between contact with the triggering agent and death is a very short 5-10 minutes. Fatal anaphylaxis due to foods usually leads first to dyspnea and then to respiratory failure. Allergic bronchial asthma represents a major risk factor. Knowledge of the allergens capable of triggering life-threatening and fatal anaphylaxis makes it easier for the physician to assess the risk potential when confronted by an emergency situation.

Anaphylaxis↗
PubMed2006

Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: Implications for anti-inflammatory activity of antihistamines.

BACKGROUND: Desloratadine is an H1-histamine antagonist which possesses additional anti-inflammatory properties through inhibition of leukocyte activation and reduction of ICAM-1 expression on mucosal epithelial cells. So far no studies have addressed the potential anti-inflammatory activities of desloratadine and loratadine on skin keratinocytes. OBJECTIVE: In this study the capacity of desloratadine and loratadine to counteract human keratinocyte activation by interferon-gamma (IFN-gamma) was analyzed. In particular, the chemokine release of kerationcytes and the crosstalk between keratinocytes and lymphocytes were examined. METHOD: Keratinocyte cultures established from normal skin of healthy donors were activated by IFN-gamma in the absence or presence of desloratadine and loratadine, and tested for the release of CCL5/RANTES, CXCL8/IL-8, CCL17/TARC and CXCL10/IP-10. Furthermore the supernatants of differentially stimulated keratinocytes were used for migration studies of human neutrophils, eosinophils and polarized Th1/Th2 clones. RESULTS: Desloratadine and loratadine inhibited the constitutive and IFN-gamma-induced release of CCL5, CXCL8 and CXCL10 from keratinocytes, while the low release of CCL17 remained unchanged. Furthermore the crosstalk between lymphocytes and keratinocytes was blocked as shown by a reduced capacity of desloratadine/loratadine-stimulated keratinocytes to attract human neutrophils, eosinophils and T cells. CONCLUSIONS: The results indicate that desloratadine has the capacity to block the IFN-gamma-induced activation of keratinocytes, and that it can thus exert important regulatory effects on cell-mediated immune responses in the skin. The rather high doses required for these effects argue for a topical application when trying to use desloratadine in epidermal inflammatory conditions.

Anti-Inflammatory Agents↗
PubMed2006

[Follicular drug reaction from cetuximab: a common side effect in the treatment of metastatic colon carcinoma].

Cetuximab belongs to a newly developed group of anti-cancer drugs, which have an inhibitory effect on the epidermal growth factor receptor (EGF-R). EGF-R plays a major role in the homeostasis of the epidermis and epidermal appendages. In addition, EGF-R is expressed on a variety of carcinomas of different origin and is thought to be partly associated with tumor progression. For this reason, inhibition of EGF-R seems a promising anti-cancer therapy, as shown in a few clinical trials. As a side effect of the therapy, a follicular rash often develops in the seborrheic areas; this cutaneous reaction is associated with longer survival. We present a typical case and discuss the important features of the follicular rash occurring after EGF-R inhibition.

Anaphylaxis↗
PubMed2006

Current eczema in children is related to Der f 1 exposure but not to Der p 1 exposure.

BACKGROUND: Mite allergen exposure is an important risk factor for specific IgE production and is associated with asthma, hay fever and eczema. Whether these associations are independent of mite species has not been investigated so far. OBJECTIVES: To investigate the influence of exposure to the major house dust mite (HDM) allergens Der p 1 and Der f 1 on sensitization, respiratory symptoms, and especially on eczema and related skin symptoms in 6-7-year-old children. METHODS: In a cross-sectional study in Augsburg (Bavaria, Germany) 1669 school beginners (mean age 6.5 years) were investigated in 1996. The concentrations of Der p 1 and Der f 1 were measured in dust samples from mattresses of 1081 children by enzyme-linked immunosorbent assay. The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and determination of specific serum IgE concentrations by radioallergosorbent test. Information about covariates was taken from questionnaires and interview data. Logistic regression was used to adjust for confounding. RESULTS: The mean concentrations of Der p 1 and Der f 1 were 0.68 and 0.79 microg g(-1) dust, respectively. The relationship between the two species-specific allergens in individual homes was poor (Pearson correlation 0.2). Influencing variables were bedroom-sharing (Der p 1) and social status of the parents (Der f 1). Respiratory diseases were positively associated with both allergen concentrations [odds ratio (OR) between 1.1 and 2.6]. These associations were significant for sneezing attacks (Der p 1 and Der f 1). Reported prevalence of current (in the last 12 months) itchy skin rash was significantly associated with exposure to Der f 1 only (OR 2.4, P < 0.003); also a diagnosis of atopic eczema on the day of investigation was positively associated with Der f 1 only (OR 1.8, P = 0.14). CONCLUSIONS: Studies on the effects of HDM exposure on eczema and allergies should consider specific effects of different mite species. This might have implications on assessment of allergen exposure and consecutive prevention or therapeutic measures.

Allergens↗
PubMed2006

The course of eczema in children aged 5-7 years and its relation to atopy: differences between boys and girls.

BACKGROUND: The role of atopy in the pathophysiology of eczema is still under debate. The concept and analyses of the nonatopic and atopic subtypes of eczema have gained increasing interest in recent studies. The course of these subtypes and differences between boys and girls have not been investigated so far. OBJECTIVES: To examine the course of nonatopic and atopic eczema in preschool children from Germany with regard to sex. METHODS: Repeated cross-sectional studies were performed in 5-7-year-old preschool children from Germany between 1994 and 2000. Individuals with eczema were identified by a dermatological examination. In addition to a questionnaire, skin prick tests and analyses of serum IgE antibodies against seven and five environmental allergens, respectively, were performed. Atopy was defined by sensitization to at least one of five common aeroallergens (birch, grass and mugwort pollen, house dust mites, cat dander). In part of the study population investigations of spare time behaviour and skin function were carried out (including stratum corneum hydration and skin surface pH). RESULTS: A total of 2693 girls and 2783 boys underwent a full dermatological examination of the skin and determination of sensitization. Among the girls, 8.7% demonstrated eczema clinically at the day of investigation in contrast to 6.1% of the boys. In girls, early onset eczema (< 2 years of age) was strongly related to atopy at age 5-7 years [odds ratio (OR) 3.7; 95% confidence interval (CI) 2.7-5.1], whereas late-onset eczema (> or = 2 years of age) was not (OR 1.0; 95% CI 0.7-1.5). Boys were more often atopic at the age of 5-7 years than girls (28.3% vs. 20.6%), and early and late-onset eczema were related to atopy without such a difference (OR 2.8, 95% CI 2.0-4.0; OR 1.9, 95% CI 1.3-2.8, respectively). The excess of current eczema in 5-7-year-old girls compared with boys was related to the nonatopic type. The higher susceptibility of girls in that age group to develop eczema was reflected by the skin physiological examination: even girls without eczema had significantly higher skin surface pH and lower stratum corneum hydration than boys. Additionally, questionnaire data revealed that girls more often than boys predominantly played indoors, which was associated with more eczema. CONCLUSIONS: Atopy and eczema develop differently in boys and girls. Boys are more often atopic, whereas girls suffer significantly more often from eczema without relation to atopy. The nonatopic type of eczema in preschool girls is noticed predominantly after their second birthday. Genetic and lifestyle factors may contribute to this difference.

Age of Onset↗
PubMed2006

Intercellular adhesion molecule-1: a consistent inflammatory marker of the cutaneous radiation reaction both in vitro and in vivo.

BACKGROUND: Radiation damage to skin is a key diagnostic and prognostic parameter for patients accidentally exposed to radiation. Moreover, skin is a target organ for crucial side-effects of routine radiotherapy. The pathophysiology of the cutaneous radiation reaction is in many respects still unknown. The acute inflammatory radiation reaction of skin has been shown to involve alterations in cell-cell and cell-matrix interactions, which are mediated by cellular adhesion molecules. OBJECTIVES: To evaluate the effect of ionizing radiation on intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells. METHODS: Dermal monolayer cells, a three-dimensional skin model and skin biopsies were investigated for ICAM-1 expression after ionizing radiation using flow cytometry, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with protein kinase inhibitors and dexamethasone prior to irradiation was analysed by flow cytometry. RESULTS: Using different sources of skin cells, we demonstrated a consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing radiation. Blocking experiments revealed that tumour necrosis factor-alpha, another ICAM-1 inducer, does not account for the effect of radiation. Radiation-induced upregulation of ICAM-1 expression was significantly attenuated by inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38 MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting its usefulness to treat the cutaneous radiation reaction. CONCLUSIONS: Our data suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous radiation reaction both in vitro and in vivo that might provide new therapeutic options for diagnosis and treatment of effects of radiation.

Aged↗
PubMed2006

Influence of short-term exposure to airborne Der p 1 and volatile organic compounds on skin barrier function and dermal blood flow in patients with atopic eczema and healthy individuals.

BACKGROUND: Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available. OBJECTIVE: We investigated the effect of airborne VOCs on the skin of patients with AE and controls in the presence or absence of house dust mite allergen, Der p 1. METHODS: In a double-blind crossover study, 12 adults with AE and 12 matched healthy volunteers were exposed on their forearms to Der p 1 and subsequently to a mixture of 22 VOCs (M22, 5 mg/m(3)) in a total body exposure chamber for 4 h. Transepidermal water loss (TEWL) and skin blood flow were measured in all subjects before, during and after exposure. Additionally, an atopy patch test (APT) with Der p 1 was applied to the skin after exposure. RESULTS: A significant increase in transepidermal water loss was observed 48 h after exposure to VOCs as compared with exposure with filtered air in all individuals (mean difference: +34%; 95% Confidence Interval: 7-69%). Prior Der p 1 exposure resulted in a significant rise of dermal blood flow after 48 h in patients with AE but not in controls. Six out of seven patients showed enhanced atopy patch test (APT) reactions to HDM allergen after previous exposure to VOCs. CONCLUSION: Our results show that exposure to VOCs - at concentrations commonly found in indoor environments - can damage the epidermal barrier and enhance the adverse effect of Der p 1 on sensitized subjects with AE. These findings may contribute to a better understanding of the mechanisms underlying the increase in prevalence and exacerbation of AE.

Adult↗
PubMed2006

Comparison of basophil activation tests using CD63 or CD203c expression in patients with insect venom allergy.

BACKGROUND: Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. OBJECTIVE: It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. MATERIALS AND METHODS: 43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. RESULTS: The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. CONCLUSION: These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

Allergens↗
PubMed2006

Efficacy and functionality of silver-coated textiles in patients with atopic eczema.

BACKGROUND: Microbial skin colonization with Staphylococcus aureus is known to play an important role in atopic eczema (AE). Recently, an antibacterial effect of silver-coated textiles on S. aureus colonization has been demonstrated. OBJECTIVES: To investigate clinical efficacy and functionality of silver-coated textiles in AE, a multicentre, double-blind, placebo-controlled trial was conducted. PATIENTS/METHODS: From November 2001 to August 2002, 68 consecutive outpatients clinically diagnosed with generalized AE were included in the study. Inclusion criteria were the clinical diagnosis of AE with a moderate severity as measured by the scoring of atopic dermatitis (SCORAD) index with at least 20. Patients were instructed to wear either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. Only basic skin care and ongoing therapy with topical steroids or oral antihistamines was permitted. Clinical severity was assessed using the 'SCORAD' before, during and at the end of study. Quality of life (QOL), wearing comfort (WC) and functionality (FU) of study clothes were measured in parallel. Patients documented their subjective and objective symptoms daily. RESULTS: In the verum group, eczema improved significantly after 1 week with further enhancement until the end of study (P = 0.03 and P < 0.001). Silver-coated textiles were comparable to cotton in WC and FU. Pruritus and self-assigned skin condition improved significantly more than with placebo (P < 0.001 and P = 0.003). CONCLUSIONS: In conclusion, silver-coated textiles are able to improve objective and subjective symptoms of AE significantly within 2 weeks, showing a good wearing comfort and functionality comparable to cotton.

Adolescent↗
PubMed2006

Atopic eczema: what's new?

Atopic eczema (AE) is a chronic inflammatory skin disease characterized by recurrent intense pruritus and a typical age-related distribution of skin lesions. Several new aspects with regard to the pathogenetic background as well as strategies for prevention, diagnosis and treatment of AE have emerged. There are ongoing studies on genetic susceptibility loci, as well as environmental and nutritional factors associated with an increase or a decrease of AE lesions. The atopy patch test is now available for identification of allergens in aeroallergen-triggered AE. New topical therapies, such as the calcineurin inhibitors, have broadened the therapeutic armamentarium substantially. In order to increase knowledge and coping strategies, patient education programs have been launched. Learning objective Upon completing this paper, the reader should be aware of new developments in AE, especially on nomenclature, prevention strategies, diagnostic tests, as well as therapeutic options.

Animals↗