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Notes: We report the results of an open, prospective study on the efficacy of systemic ranitidine in the treatment of psoriasis. Twenty patients suffering from moderate to severe psoriasis were included in the study. The median pretreatment PASI score was 15·7 (range 6·0-24·7). The patients were treated with oral ranitidine 300 mg twice a day for 6 months; no other medication was allowed during the study period. Eighteen patients completed the study. The median PASI score was reduced from 15·7 to 14·5. 9·1 and 5·7. after 1, 3 and 6 months of treatment, respectively (P〈0·00001). A significant reduction in PASI score was evident at 3 months of treatment. A mild to moderate deterioration occurred in 15 patients within the first month of treatment, but this was followed by improvement during prolonged treatment in most patients. No other clinical and/or biochemical side-effects were observed. Eight patients continued therapy with ranitidine after the study was completed, and none of these patients relapsed during a follow-up period of 12–18 months. The results of the present study suggest that ranitidine may be a beneficial and safe treatment for psoriasis. In addition, high-dose, long-term ranitidine treatment appears to be free from severe adverse effects.

Notes: To study the human intestinal mast cell of children and adults, we combined a sensitive glassfibre-based histamine assay with the enzymatic and mechanical dispersion of surgical specimens or mucosal biopsies. The method yields between 1.2 × 103 to 4.6 × 103 mast cells/mg tissue constituting 1.2% to 5.3% of total cell count. The mast cell yield, however, depends on the intestinal tissue specimen used for dispersion. Aliquots containing 1500 mast cells per sample are sufficient for measuring significant amounts of histamine (± 0.15 ng histamine per sample), thus making it possible, to carry out approximately 75 tests for four mucosal biopsies of 10 mg each. The intestinal mast cell releases histamine in a dose-dependent manner on challenge with anti-IgE (6–600 U/ml), ionophore A23187 (0.25–1.0 μM), and Concanavalin A (0.7–25.0 μg/ml). The histamine release shows interindividual variation with a net histamine release between 0 to 2.5 ng/samples dependent on the secretatogue. In general, it is not necessary to passively sensitize the mast cells to obtain a sufficient histamine release response to anti-IgE challenge, indicating the presence of intact and functional cell-bound IgE. However, it is shown that four of 10 non-atopic intestinal mast cell samples could be passively sensitized with human plasma containing either mite- or grass-specific IgE without stripping off the IgE first. This indicates the presence of free and preserved Fc-receptors on the dispersed mast cells in some subjects. In addition, it is found that the phorbolester TPA increases the histamine release response to A23187 and turns anti-IgE non-responding mast cells into responding mast cells, but TPA alone at 2 to 16 ng/ml has no histamine releasing effect. In patients with anti-IgE responding mast cells no additional effect of TPA is seen. Finally, no substantial differences between mast cells of children and adults are demonstrated.

Notes: The in vitro histamine release response of human intestinal mast cells and basophils challenged with anti-IgE, Concanavalin A, ionophore A23187 and food extracts was compared with skin prick test, RAST analysis and open food challenge. It was not possible to perform food challenge in all patients; however, seven children underwent open food challenge and in five the clinical diagnosis of “true” food allergy was confirmed. The intestinal mast cells were pooled from enzymatically dispersed duodenal biopsies obtained by duodenoscopy from 15 selected children suspected of food allergy, and five age-matched controls. In nine of 10 patients classified as “food allergic” intestinal mast cells released histamine to various food extracts in a dose-dependent fashion. From the mast cells of the nine food-allergic patients compared with non-allergics, the anti-IgE mediated mast cell histamine release was increased. Additionally, at 1000 U/ml anti-IgE the mast cell histamine release was increased compared with their corresponding basophils. However, in non-allergic subjects the histamine release of basophils was increased compared with their corresponding mast cells. Histamine release from basophils was positively correlated to the test scores of the RAST analysis, skin prick test, and food challenge. No apparent correlation between tests scores obtained from histamine release of intestinal mast cell and the other tests was demonstrated, except in children with diarrhoea as only symptom. However, the study gives evidence that duodenal mast cells actually are sensitized with specific IgE and thus may play a pathophysiological role in food hypersensitivity. In addition, the study shows that the ability of different stimuli, including food extracts, to trigger basophil histamine release does not correlate with their potency to induce histamine release from mast cells.

Notes: AIDS patients in contrast to healthy individuals show basophil histamine release by stimulation in vitro of their blood leukocytes with Candida albicans (CA) and Herpes simplex virus Type I (HSV-I). Passive sensitization of cells from healthy individuals with the patient serum or surface immunoglobulins (Ig) derived from leukocytes of AIDS patients caused histamine release by the following stimulation of the cells with CA or HSV-I. When IgE was removed from the surface Ig no response was obtained, whereas a removal of IgG did not diminish the response. In contrast, no passive sensitization was obtained by serum derived from healthy individuals. The results show that IgE is responsible for the histamine release caused by CA and HSV-I in AIDS patients.

Notes: The inhibitory capacity of calcium antagonists on basophil histamine release was examined in allergic patients and in controls. All dihydropyridines tested (nifedipine, nimodipine, nitrendipine, nicardipine, felodipine) dose-dependently inhibited anti-IgE- and A23187-induced release with an order of potency of felodipine 〉 nicardipine 〉 nifedipine = nimodipine = nitrendipine. Only the inhibition induced by felodipine and nicardipine on anti-IgE-induced release could be counteracted by increasing extracellular calcium. Diltiazem, not belonging to the dihydropyridines, was a weak inhibitor. A combination of felodipine and verapamil in low concentrations exerted a synergistic inhibitory effect on histamine release, whereas this was not the case with other combinations of antagonists. The results suggest differences in the mode of action of the 1.4-dihydropyridines. This might be of significance in the search for calcium antagonists suitable in the treatment of allergic diseases.

Notes: Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionphore A23187, whereas the release induced by S. aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane sialic acid in basophil leukocytes is involved in the regulation of histamine release, possibly by a modulation of the trans-membraneous calcium fluxes preceding histamine release.

Notes: The histamine-releasing capability of lipopolysaccharides (LPS) was examined in human leukocyte suspensions. LPS alone did not release histamine, but was found to enhance the histamine release caused by anti-IgE. Also the IgE-mediated histamine release caused by specific antigens (allergens or bacteria) in sensitized individuals was enhanced by LPS. The potentiating effect of LPS was observed in grass pollen and dog dander allergic patients as well as in patients sensitized to E. coli or Staph, aureus bacteria. No potentiation was obtained by exposure to unspecific allergens or bacteria to which the persons were not sensitized. Bacteria can release histamine by immunological or nonimmunological mechanisms, and only the immunological histamine release was found to be potentiated by LPS. It is speculated that endotoxins reinforce release of histamine caused by allergens in allergic patients or by bacteria in persons sensitized to these microorganisms.

Notes: Levels of specific serum IgE to cow's milk, whole hen's egg, egg white, and egg yolk were compared to the outcome of double-blind, placebo-controlled food challenge ‘DBPCFC) with fresh egg and/or milk in 21 adults with a case history of immediate hypersensitivity to egg and/or milk. Specific serum IgE was measured by four different commercially available tests and by an inhouse Maxisorp RAST using freshly prepared food extracts. Sensitivities and negative predictive accuracies were generally high with egg white and milk, but low with egg yolk. Specificities and positive predictive accuracies were low for all allergens and tests. Changing the cutoff levels did not improve the ability of the tests to predict clinical allergy. Among commercially available test allergens, egg white gave the most consistent results in levels and class scores, and the highest degree of concordance with DBPCFC, whereas egg yolk and milk varied more. Applying freshly prepared food extracts in Maxisorp RAST did not improve diagnostic value. Measuring specific serum IgE levels in control subjects tolerant to egg/milk showed that false positive reactions occurred frequently among patients with another food allergy and atopic dermatitis, whereas most tests were likely to be negative in pollen-allergic and nonallergic volunteers. In conclusion, specific IgE measurements with egg white and milk were useful for exclusion of symptomatic hypersensitivity to egg and milk in patients with a positive history, whereas DBPCFC is still mandatory in patients with positive history and positive test. Measuring egg-yolk-specific IgE or using freshly prepared food extracts for specific IgE measurements added no further diagnostic information. The rate of clinically insignificant positive test results seems to be influenced by the prevalence of other food allergies and/or atopic dermatitis in the population under study.

Notes: The interrelation of in vitro IgE-mediated parameters, i.e. serum-specific IgE (RAST), basophil cell-bound specific IgE, and histamine release from basophil leucocytes was investigated in a 1-year placebo-controlled, double-blind Cladosporium immunotherapy study involving 22 adult asthmatics. The intense and early burst (within 6 weeks of immunotherapy) of serum-specific IgE did not result in a corresponding increased binding of specific IgE molecules to basophils. Cell-bound IgE increased in the Cladosporium season in both groups at the same time as serum levels of specific IgE declined in the Cladosporium group. In the placebo group histamine release from circulating basophils paralleled changes in basophil-bound IgE. In Cladosporium-treated patients, histamine release cell sensitivity after a lag phase (during immunotherapy dose-increase) declined two log steps, i.e. the cells became less responding in spite of a significant increase in cell-bound IgE. To further evaluate the sensitizing capacity of circulating specific IgE, passive sensitization studies were performed using basophils from a single donor. Although sera taken at the maximal IgE-response showed an enhanced capacity of passive sensitization, the ratio between RAST and passive sensitization capacity increased significantly in Cladosporium-treated patients, implying a less than expected sensitization capacity of immunotherapy-induced specific IgE. The lack of active binding of IgE to basophils might be explained by a reduced Fc-affinity of immunotherapy-induced IgE in contrast to the Cladosporium seasonally induced IgE. Regarding the decrease in histamine release in Cladosporium-treated patients in spite of an increased amount of cell-bound specific IgE, immunotherapy may initiate a decrease in mediator releasibility which is not caused by a reduction in the number of Fc-receptors but rather some yet unknown subcellular mechanisms regulating the histamine release. The described changes in IgE-mediated parameters do not seem to be caused by interference with either specific IgG, or IgG4. Changes in histamine release in the Cladosporium, season were the only IgE-mediated parameter significantly related to the graded clinical efficacy of immunotherapy.

Notes: The study aimed to determine whether occupational contact urticaria and symptoms of mucous membranes, reported by five workers in a cactus nursery, were due to IgE-mediated allergy to Schlumbergera cacti. The five persons had positive skin prick tests to the plants as is and positive histamine-release tests, and in three of them specific IgE to the cacti could be demonstrated by Maxisorp RAST and immunoblotting. Four of the patients were atopic, and the fifth had a positive skin prick test to cat dander, indicating latent atopy. Skin prick tests with cacti were negative in most atopic volunteers, and all had negative histamine-release tests. The results suggest a true IgE-mediated allergy to the cacti, and both genetic predisposition and close contact with the plants at work seem to be important factors in the emergence of this new occupational allergy.