Search PubMed⌕ Search

Biomedical subjects

J Ring

Publications and source records attributed to J Ring.

At least 217 records · Page 12Linked to original sources

Antihistamines in urticaria.

Urticaria is one of the most common and, in its chronic course, excruciating dermato-allergic diseases. Apart from the dermatological diagnosis, the identification and evaluation of causal triggering factors is of utmost importance. Here a 'three-step guideline' (according to Ring and Przybilla) has gained acceptance, ranging a general basic examination via an intensive investigation until oral provocation tests for food allergy and oral provocation tests for idiosyncrasy (OPTI) against food additives. Apart from true IgE-mediated allergies, pseudo-allergic reactions against food additives as well as food contents represent a major problem in chronic urticaria. Recently gastric mucosal colonization with Helicobacter pylori as the trigger of chronic urticaria has received attention. New pathophysiological concepts describe autoantibodies that are directed either against IgE or against the high-affinity IgE-receptor on the surface of mast cells and basophil leucocytes. In the intradermal test with autologous serum positive wheal and flare reactions can be observed (Greaves' test). In many patients with chronic urticaria considerable psychosomatic involvement is also observed. Histamine is one of the major mediators of most forms of urticaria although in some cases, especially physical urticaria, other mediators seem to play a role. Therefore antihistamines, and mainly H1 antihistamines, are the mainstay of antiurticaria therapy. Some studies have shown a benefit of combined H1- and H2-antagonist treatment in special forms of urticaria namely urticaria factitia. Similarly pretreatment with combined H1 and H2 antagonists has been proven to reduce effectively the frequency of pseudo-allergic reaction to some histamine-releasing drugs used in radiology or surgery. More than 50 years after the first introduction of an antihistamine into allergy therapy, antihistamines still represent modern and exciting agents contributing to the continuous improvement of antiallergic therapy. Antihistamine therapy can be performed with either the classical or second generation antihistamines. Classical antihistamines are connected with considerable side-effects especially sedation and anticholinergic effects. New non-sedating antihistamines have been developed that do not cross the blood-brain barrier. The efficacy of mizolastine, a new non-sedating H1 antagonist, has been evaluated in several placebo-controlled and comparative clinical trials. Overall, mizolastine 10 mg/day was found to be significantly more effective than placebo and as effective as other second generation antihistamine drugs in the management of patients with chronic urticaria, with a rapid and sustained action.

Benzimidazoles↗

Atopy patch test reactions are associated with T lymphocyte-mediated allergen-specific immune responses in atopic dermatitis.

BACKGROUND: Positive test reactions to epicutaneous application of aeroallergens served as a model of 'early' eczema in atopic dermatitis (AD) in a number of dermato-immunological studies. However, no quantitative evaluation has been performed so far comparing specific T-cell activation parameters in the peripheral blood of AD patients with positive or negative atopy patch tests (APT). OBJECTIVE: The purpose of this study was to investigate specific immunological parameters in patients with atopic dermatitis showing positive or negative atopy patch tests reactions. METHODS: APT results (n = 96) were compared with allergen-specific IgE, specific lymphocyte proliferation, and the expression of 'activation' markers on peripheral blood T-cells upon in vitro stimulation with house dust mite, cat or grass pollen allergens. RESULTS: Only a subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE > 0.7 kU/L) developed APT-reactions to the corresponding allergen. APT reactions were, however, significantly associated with allergen specific lymphocyte proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T-cells (p < 0.05) upon in vitro stimulation. CONCLUSION: The association of delayed skin reactions with allergen specific T-cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.

Allergens↗

Immunohistochemical investigation of the cellular infiltrates at the sites of allergoid-induced late-phase cutaneous reactions associated with pollen allergen-specific immunotherapy.

BACKGROUND: Reduction in the size of the allergen-induced late-phase reaction (LPR) is seen as a consequence of successful allergen specific immunotherapy. OBJECTIVE: It was the aim of this study to characterize the cellular infiltrate at the sites of cutaneous LPR that may occur following injection of a depot pollen allergoid (Allergovit(R)) during immunotherapy and thereby determine the immunological nature of the response. METHODS: Punch biopsies were taken 24 h after subcutaneous injection of a depot pollen allergoid from eight patients that showed LPR and a further five patients that did not. Additional biopsies taken 24 h after injection of allergoid-free depot in the same patients served as controls. Immunoenzymatic labelling of the cryostat sections with different antibodies was performed with the APAAP technique. Results were expressed as cells/field (400 x magnification). RESULTS: Similar dermal cellular infiltrations were seen following depot allergoid injections in patients both with and without LPR. Patients with LPR showed statistically significant increases in total cells, CD4+ cells, CD11c+ cells, CD45RO+ cells, CD45RB+ cells and activated eosinophils at the reactions sites as compared with control sites. In patients without LPR CD11c+ cells, HLA-DR+ cells and CD45RA+ T cells increased significantly. CD8+, CD1a+, NP57+, CD23+ and CD25+ cells did not differ significantly in either group. CONCLUSION: These results indicate that activation of T cells, monocytes/macrophages and eosinophils at the sites of LPR following injection of depot allergoid are comparable with those following injection of allergen. Even in the absence of a cutaneous LPR, subsets of T cells and monocytes/macrophages increased. These cell activations may reflect events associated with the mechanisms of allergoid-based specific immunotherapy, and suggest that at least part of the late-phase reaction may be independent of IgE.

Adult↗

Stromelysin-3 (ST-3): immunohistochemical characterization of the matrix metalloproteinase (MMP)-11 in benign and malignant skin tumours and other skin disorders.

Matrix metalloproteinases (MMP) are involved in remodelling of the extracellular matrix (ECM) proteins suggesting that they play an important role in inflammatory process, in tumour invasion and metastasis. We examined immunohistochemically 330 cases of different skin disorders with the monoclonal antibody against MMP 11, stromelysin-3 (ST-3) protein. We found a positive immunoreactivity in fibroblasts surrounding malignant epithelial tumour cells in 63 of 125 cases (50.4%) of basal cell carcinomas, in four of 25 (16%) squamous cell carcinomas, whereas the tumour cells themselves were negative. Furthermore, the ST-3 protein could be detected in 23 of 40 cases (57.5%) of dermatofibroma, in two of five cases (40%) of atypical fibroxanthoma, in one of eight cases (12.5%) of dermatofibrosarcoma protuberans and, locally, in one of 10 cases (10%) of malignant fibrous histiocytoma. It was not present in the following skin lesions: keratoakanthomas (n = 12), Bowen's disease (n = 10), malignant melanoma (n = 12), melanocytic nevi (n = 28) and Kaposi's sarcomas (n = 25). In eczema (n = 10), psoriasis (n = 10) and virus-induced tissues (i.e. condylomata acuminata, n = 10) we did not observe an expression of ST-3 protein. We conclude first that ST-3 protein is a fibroblastic factor expressed in stromal cells adjacent to carcinoma cells; second, that ST-3 protein seems to be associated with benign fibroblastic tumours; and third, that it does not play a role in eczema, psoriasis or virus-induced skin lesions.

Basal Cell Carcinoma↗

Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema.

The non-involved skin of atopic eczema (NEAE) is characterized by severe dryness and an impaired barrier function of the stratum corneum as indicated by an increased transepidermal water loss. Previous studies have demonstrated that this barrier impairment coincides with marked alterations in the amount and composition of stratum corneum ceramides. The aim of this study was to identify specific alterations in NEAE that may be used in the diagnosis of the atopic eczema. Using a classical procedure for high performance thin layer chromatography we could confirm earlier results: apart from Cer(EOH), which contains omega-hydroxy fatty acid (O) ester-linked to linoleic acid (E) and amide-linked to 6-hydroxy-4-sphingenine (H), the quantities of all ceramide fractions were significantly decreased. Furthermore, Cer(EOH)/Certotal was significantly increased, whereas the percentage of Cer(EOS), which contains sphingosine (S), and Cer(NP), which contains non-hydroxy fatty acid (N) amide-linked to phytosphingosine (P), were significantly decreased. Using a modified procedure for high performance thin layer chromatography we could demonstrate the formation of a double peak in the position of Cer(AS), which contains alpha-hydroxy fatty acid (A), in lipids of NEAE. The subfractions of the double peak comprised 15% and 12% of Certotal. MALDITOF mass spectrometry suggested that the double peak was formed by a homologous series of mono-hydroxylated and mono-unsaturated ceramides of different chain length, e.g., Cer(AS) subfractions containing either (C16,18) or (C22,24,26) alpha-hydroxy fatty acids. In contrast, in normal skin a single peak in Cer(AS) position, which comprised 22% of Certotal, was mainly formed by the long chain subfraction. In some cases this single peak displayed a small shoulder at its right flank, but never showed a clear peak separation when developed with NEAE samples. Furthermore, even in senile xerosis, or in either non-involved skin of psoriasis or seborrhoic eczema, only a single peak occurred in Cer(AS) position. Accordingly, the double peak might be specific for NEAE and turn out to be a marker for atopic eczema.

Ceramides↗

Bioavailability investigation of a new tilidine/naloxone liquid formulation compared to a reference formulation.

An oral solution available as ethanol-free droplets of the fixed drug combination tilidine-HCl 50 mg/naloxone-HCl 4 mg (CAS 27107-79-5 and CAS 465-65-6, respectively; Tilidin-ratiopharm plus Tropfen) was investigated in 12 healthy volunteers together with an ethanol-containing reference preparation for comparable bioavailability. The study was conducted in an open, randomized, two-way cross-over design applying single doses of 20 droplets (equivalent to 50 mg tilidine-HCl/4 mg naloxone-HCl) of either formulation in the fasting state. The drug plasma profiles were monitored for a period of 48 h by means of LC-MS/MS for tilidine and its active metabolite nortilidine, whereas GC-MS was employed in order to determine naloxone and its phase I metabolite, 6-beta-naloxole. Maximum concentrations (Cmax) achieved were 22.28 ng/ml (tilidine) and 92.78 ng/ml (nortilidine) for the test preparation. Corresponding values for the reference preparation were 24.95 ng/ml (tilidine) and 100.73 ng/ml (nortilidine). The extent of drug absorption (AUC0-infinity) amounted to 38.83 ng h/ml and 467.63 ng h/ml for the prodrug tilidine and the metabolite nortilidine of the test preparation and corresponded well to 43.81 ng h/ml and 493.85 ng h/ml of the reference. Regarding the rate of drug absorption, essentially identical tmax and Rabs values for both tilidine and nortilidine of either preparation in addition pointed to well comparable liquid formulations and equipotent analgesia may be inferred from opioid pharmakokinetic profiles. Pharmacokinetics of the opioid antagonist naloxone and 6-beta-naloxole were also determined and resulted in well coinciding profiles for both preparations. Thus despite the fact that only minimum oral naloxone bioavailabilities were observed, plasma level monitoring of naloxone and 6-beta-naloxole allowed for demonstration of systemic exposure of opioid antagonistic compounds throughout a period of 2-3 h after oral drug administration. Due to the limited number of subjects involved, the primary aim of the study did not consist in demonstration of drug bioequivalence. Rather a comparable bioavailability between preparations was assumed if AUC and Cmax point estimators of 90% confidence intervals would be contained within a 0.80-1.20 range. The study outcome revealed that all four investigated analytes met this requirement, whilst nortilidine pharmacokinetic parameters even fulfilled commonly accepted bioequivalence criteria, i.e. inclusion of 90% confidence intervals of AUC- and Cmax-ratios within acceptance limits of 80% and 125%. Increased data variation observed with bioavailability parameters of tilidine, naloxone and 6-beta-naloxole prevented their bioequivalence demonstration based on only 12 study participants. In conclusion, single doses of two different tilidine/naloxone 50 mg/4 mg liquid formulations revealed well comparable bioavailability for all 4 analytes investigated. Both treatments were fairly well tolerated. Most frequently reported adverse events were dizziness, headache and nausea, which all recovered without sequelae and necessity of concomitant treatment.

Adult↗

Airway diseases and allergies in East and West German children during the first 5 years after reunification: time trends and the impact of sulphur dioxide and total suspended particles.

BACKGROUND: East-West comparison studies in Europe find higher prevalences of infectious airway diseases and lower prevalences of allergies in eastern areas. Pollution from sulphur dioxide (SO2) or total suspended particles (TSP) are discussed as causes of this difference. METHODS: In four differently polluted areas of East Germany where pollution decreased dramatically between 1989 and 1995 cross-sectional studies in about 7-year-old children were repeated every year between 1991 and 1995. In two differently polluted areas of West Germany studies with the same design were done in 1991 and 1994. In all, 19090 children participated in the study. Thirteen different questions about airway diseases and allergies were evaluated. Logistic regression was used to adjust for confounding. RESULTS: With the exception of pneumonia, all infectious airway diseases and irritations of the airways show a steeper temporal decrease in East than in West Germany or are positively associated with either SO2 or TSP in East Germany. For allergies and related symptoms no differences in time trends could be detected or no association with SO2 or TSP could be seen in East Germany. CONCLUSION: Most airway diseases were more frequent in East than in West Germany in 1991 and were associated with SO2 or TSP. The decrease in these pollutants between 1991 and 1995 has already had a favourable effect. An effect of SO2 or TSP pollution on allergies and related symptoms could not be detected. This pollution does not protect against the development of allergies.

Age Distribution↗

The clinical expression of allergy in the skin.

The cutaneous immune system has evolved to protect the organism from potential exogenous pathogens in a complex manner. Recent investigations of the special role of the skin in allergy have focused on the proinflammatory potential of various cells such as Langerhans' cells, keratinocytes, mast cells (MC), endothelial cells, and dermal fibroblasts. Furthermore, in processing and reacting to antigens, infiltrating inflammatory cells (lymphocytes; monocytes; macrophages; and eosinophil, neutrophil, and basophil granulocytes) play an important role both by cell-cell interactions with specific receptors on cell surfaces and via soluble mediators.

Antigen Presentation↗

Suppression of immediate-type hypersensitivity elicitation in the skin prick test by ultraviolet B irradiation.

Reproducibility of skin prick testing (SPT) and its modulation by ultraviolet B (UVB) radiation is of clinical interest. Sensitized atopic volunteers (groups A and B, n=21) were prick tested with common commercial allergen solutions (undiluted, diluted 1:10 and diluted 1:100) before, 24 h after one and 24 h after three suberythematous UVB irradiations. Volunteers in group A (n=8) received local UVB irradiation of prick test areas, whereas volunteers in group B (n=13) received whole body UVB irradiation, with prick test areas covered. In group A, the wheal intensities, expressed as the ratio allergen wheal size to histamine wheal size, were decreased by 28% (1:10 dilution) (P=0.01) and 45% (1:100 dilution) (P=0.02) after one UVB irradiation. Flare intensities were decreased by 48% (1:10 dilution) (P=0.03) after three UVB irradiations. In group B, the wheal and flare responses tended to decrease. Possible mechanisms of this short-term suppressive effect of UVB irradiation on SPT reactions include a direct effect on mast cells. It is concluded that UV irradiation, even a single exposure, prior to skin testing may compromise the validity of SPT testing.

Adult↗

The Dyshidrotic Eczema Area and Severity Index - A score developed for the assessment of dyshidrotic eczema.

BACKGROUND: Dyshidrotic eczema of the palms and soles is a common condition, which can be rather resistant to treatment. Therapy studies and their comparability are of clinical importance. OBJECTIVE: As standardized assessment methods for the severity of this particular form of eczema are lacking, we developed a severity index for dyshidrotic eczema. METHODS: The Dyshidrotic Eczema Area and Severity Index (DASI) is based on the severity grade of single items - number of vesicles per square centimetre (V), erythema (E), desquamation (S) and itch (I) - and the extension of the affected area (A) and is calculated with defined score points (p) as: DASI = (pv + pE = pS + pI) x pA. RESULTS: In two treatment studies on dyshidrotic hand eczema, the DASI was found to be a simple and useful tool to assess the severity of dyshidrotic eczema and the effect of therapy. CONCLUSION: The DASI needs to be further validated in larger cohorts.

Eczema, Dyshidrotic↗

Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus-aureus-colonized atopic eczema.

BACKGROUND: In atopic eczema (AE), skin colonization with Staphylococcus aureus plays a possible role in the pathophysiology of the disease. METHODS: Thirty-eight patients with AE were screened for their cutaneous colonization with S. aureus. The antibacterial and clinical efficacy of topical therapy with the antiseptic dye gentian violet, a potent glucocorticosteroid or a tar solution (liquor carbonis detergens) was evaluated in vivo in 21 patients with a density of >10(4) CFU/cm(2) and in vitro. Skin sites were treated twice daily for 4 days with the active drug or a corresponding control. Quantification of S. aureus was done daily during therapy as well as 3 days thereafter. The severity of the lesions was rated by a regional SCORAD. RESULTS: In gentian-violet-treated skin, bacterial density decreased significantly in lesional (p < 0.001) and unaffected skin (p < 0. 001). Bacterial densities did not decrease during therapy with glucocorticosteroid or liquor carbonis detergens but dropped afterwards. All therapeutics reduced the severity score, reduction being greatest for the glucocorticosteroid and lowest for liquor carbonis detergens. In vitro, a high antibactericidal efficacy was demonstrated only for gentian violet. CONCLUSIONS: Antibacterial therapy with gentian violet not only reduces S. aureus dramatically, but also reduces the severity of the eczema. Reduction of S. aureus after therapy with glucocorticosteroids and LCD seems to be secondary to improvement of the skin condition.

Administration, Topical↗

Positive skin tests in late reactions to radiographic contrast media.

In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients.

Angiography↗