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Biomedical subjects

G W Canonica

Publications and source records attributed to G W Canonica.

At least 163 records · Page 9Linked to original sources
PubMed1995

Follicular thyroid cells of autoimmune thyroiditis may coexpress ICAM-1 (CD54) and its natural ligand LFA-1 (CD11a/CD18).

The leukocyte functional associated antigen-1 (LFA-1)-intercellular adhesion molecule-1 (CD11a-CD18/CD54) intercellular adhesion system plays a crucial role in several immunologic phenomena, including adhesion between lymphocytes and epithelial cells. In previous studies evidence for CD54 expression on thyroid follicular cells in Hashimoto's thyroiditis was provided. In this study we evaluated the possible expression of CD11a and CD18 antigens on thyrocytes of patients with Hashimoto's thyroiditis and on thyrocytes of patients with Graves' disease and simple goiter as controls; we used both alkaline phosphatase immunostaining and indirect immunofluorescence on cryostatic tissue sections. The results showed that LFA-1 (both CD11a and CD18) positivity on thyroid follicles may occur in glands of patients with Hashimoto's disease, with a pattern very similar to that of CD54: this was observed in five of seven specimens. Conversely, no positivity was observed in tissues from patients with Graves' disease or goiter: notably, isolated follicular cells from Graves' goiter tissues are induced in culture to express CD54, but not LFA-1. Using double-staining techniques, we were able to show that in specimens from patients with Hashimoto's disease, the same follicular structures coexpressed LFA-1 and CD54. Such a coexpression of the two ligands further emphasizes the possible role of this adhesion system in the pathogenesis of epithelial damage, through bidirectional interactions between thyroid epithelial cells and infiltrating LFA-1 or CD54-positive mononuclear cells.

Adult↗
PubMed1995

Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy.

The natural exposure to house dust mites causes sensitization in genetically susceptible patients. Persistent exposure of sensitized patients causes chronic inflammation, and consequently, hyperreactivity, thus promoting the development of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells triggered by allergen has been demonstrated and related to the inflammation caused by the allergic reaction. Therefore we evaluated the possible presence of inflammation (i.e., inflammatory cell infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal levels in patients with asymptomatic allergic rhinitis caused by mites, in their relatives living in the same environment, and in healthy volunteers. In addition, the possible relationship between inflammation and house dust mite allergen exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54 expression on conjunctival and nasal epithelium was detectable in allergic subjects, whereas relatives and healthy volunteers showed few inflammatory cells and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house dust mite, sufficient to cause sensitization, was found in all houses. This study demonstrates a minimal persistent inflammation at conjunctival and nasal levels constantly detectable in patients without symptoms who are sensitized to mites and continuously exposed to the natural allergens.

Adolescent↗
PubMed1995

Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens.

BACKGROUND: The detection of specific IgE antibodies to environmental allergens does not always coincide with a diagnosis of clinically evident allergic disease, because some patients with positive skin and/or in vitro test results have no symptoms related to the allergen or allergens that induced the antibodies. OBJECTIVE: In a multicenter study the optimal cutoff values for specific IgE antibody levels and skin test results that could discriminate between patients with symptomatic and those with asymptomatic allergy were determined. METHODS: IgE antibodies specific for a panel of common aeroallergens were assayed with the Pharmacia CAP System (Pharmacia, Uppsala, Sweden) in two groups of patients, a group of 267 patients with symptomatic allergy and a group of 232 with asymptomatic allergy--both with positive skin prick test results--and in a group of 243 healthy, nonallergic control subjects. The cutoff values were established by receiver operating characteristic analysis. RESULTS: A significantly higher mean specific IgE antibody value was found in patients with symptomatic allergy compared with patients with asymptomatic allergy (p < 0.001) and in patients with symptomatic allergy compared with healthy control subjects (p < 0.001). The optimal CAP System cutoff value between patients with symptomatic and those with asymptomatic allergy was 11.7 kU/L, and when seasonal allergens were compared with perennial allergens, the cutoffs were 10.7 kU/L and 8.4 kU/L, respectively. The optimal cutoff value for the skin prick test was a wheel area of 32 mm2 for seasonal allergens and 31 mm2 for perennial allergens. The skin test had a lower diagnostic value (sum of sensitivity and specificity) than the CAP System. CONCLUSIONS: Cutoff values for specific serum IgE antibody levels are likely to be useful in clinical practice to distinguish symptomatic from asymptomatic allergy in patients with positive skin test results.

Adolescent↗
PubMed1995

Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early- and late-phase reactions after allergen-specific challenge.

BACKGROUND: Allergen-specific conjunctival challenge (ASCC) is a safe and reproducible experimental model of allergic conjunctivitis and a useful tool in the evaluation of effectiveness and possible mechanisms of action of drugs commonly used in the treatment of allergic diseases. OBJECTIVE: The protective effect of cetirizine on inflammatory changes after ASCC was assessed in 12 patients with rhinoconjunctivitis caused by Parietaria judaica in a double-blind study. METHODS: After a screening ASCC was performed, patients were randomized into two treatment groups; each patient was given cetirizine (oral tablets) 10 mg twice daily, or matching placebo for 3 1/2 days in off-pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells) were performed at baseline, 30 minutes (i.e., early-phase reaction [EPR]), 6 hours, and 24 hours (i.e., late-phase reaction [LPR]) after ASCC, before and after treatment. RESULTS: The EPR clinical events and the EPR total number of inflammatory cells were significantly reduced by cetirizine compared with placebo. The LPR clinical events and inflammatory cell recruitment were reduced by cetirizine in a similar manner. Both eosinophil and neutrophil numbers were decreased by active drug in EPR and LPR. Furthermore, ICAM-1/CD54 expression was significantly reduced by cetirizine in both the EPR and LPR compared with placebo. CONCLUSIONS: This study shows that cetirizine has a protective effect on clinical and cellular EPR and LPR events (including ICAM-1/CD54 expression on epithelium) induced by ASCC.

Adolescent↗
PubMed1995

Terfenadine exerts antiallergic activity reducing ICAM-1 expression on nasal epithelial cells in patients with pollen allergy.

BACKGROUND: Rhinoconjunctivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during the pollen season. It has recently been demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during the inflammatory response which follows allergic reactions. OBJECTIVE: The aim of the present study (placebo-controlled, double-blind, randomized) was the evaluation of the antiallergic activity of Terfenadine in the model of the allergic rhinitis due to natural pollen exposure. METHODS: Two groups of patients with pollen allergy were enrolled in this study. Ten patients were treated with Terfenadine (120 mg/die) for 7 days and 10 with placebo. Evaluation criteria were: (a) clinical: signs and symptoms (recorded daily in a diary card by patients); (b) cytological: inflammatory cell count (neutrophils, eosinophils, metachromatic cells) from nasal lavage at T0 and T7; (c) immunocytochemical: ICAM-1/CD54 expression on nasal epithelial cells at T0 and T7; and (d) mediators dosage (ECP-MPO) on nasal lavage at T0 and T7. RESULTS: As opposed to the placebo group, patients treated with Terfenadine showed a significant improvement of both symptoms (P < 0.022) and signs P < 0.001), a significant reduction of inflammatory cells infiltrate (P < 0.005), of ECP levels (P < 0.002) and ICAM-1 expression on nasal epithelial cells (P < 0.005). CONCLUSIONS: In conclusion, these data demonstrate that Terfenadine exerts antiallergic activity since it is able to reduce inflammatory cell infiltrate and downregulates ICAM-1 expression.

Adolescent↗
PubMed1995

Nasal immunotherapy to Parietaria: evidence of reduction of local allergic inflammation.

Studies over 10 yr have demonstrated local nasal immunotherapy (LNIT) to be an effective treatment for rhinitis due to pollens and mites. The aim of our work was to investigate the effects of LNIT on the local inflammatory phenomena, employing the model of nasal allergenic challenge, since no evidence has been yet provided about LNIT effects on the events due to allergic reactions. We evaluated, in addition, the possible effects of LNIT on some systemic immunologic parameters and its clinical efficacy. The study involved a double-blind, placebo-controlled trial of preseasonal immunotherapy with Parietaria in 20 adults. A significant reduction of symptoms, inflammatory infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression on epithelial cells after nasal challenge was evidence as long-lasting effect. No changes in serum allergen-specific IgE, IgG, and soluble eosinophil cationic protein were detected, whereas an unexpected increase of soluble ICAM-1 was found in the placebo group only. The treatment was well tolerated and a significant clinical improvement under natural allergenic exposure was observed in the active group. The present study provides, for the first time, evidence that LNIT is able to modulate the nasal allergic inflammation.

Administration, Intranasal↗
PubMed1995

Oxatomide reduces inflammatory events induced by allergen-specific conjunctival challenge.

BACKGROUND: Allergen-specific conjunctival challenge is a safe and reproducible experimental model to evaluate effectiveness and possible mechanism(s) of action of drugs employed in the treatment of allergic diseases. OBJECTIVE: The protective effect of oxatomide on inflammatory changes that follow allergen-specific conjunctival challenge was assessed in 20 patients with rhinoconjunctivitis due to Parietaria judaica in a double-blind study. METHODS: After a screening allergen-specific conjunctival challenge, patients were randomized into two treatment groups, each being given oxatomide (oral tablets) at 60 mg daily or matching placebo for seven days during off-pollen season. Clinical evaluation, cytologic assessment (number of inflammatory cells and ICAM-1 expression on epithelial cells) were assessed at baseline, 30 minutes, 6 hours, and 24 hours after allergen-specific conjunctival challenge, before and after treatment. In addition, electrocardiograms were obtained before and after treatment. RESULTS: Early phase reaction clinical events as well as total numbers of inflammatory cells were significantly reduced by oxatomide compared with placebo. Late phase reaction clinical events as well as total numbers of inflammatory cells were significantly reduced by oxatomide compared with placebo. ICAM-1 expression was significantly reduced by oxatomide in early phase reactions and late phase reactions compared with placebo. No pathologic cardiac events were detected in any subject. CONCLUSIONS: Oxatomide has a protective effect on clinical and cellular early phase reactions and late phase reactions (including ICAM-1 expression on epithelium) induced by allergen-specific conjunctival challenge and is safe and well tolerated.

Allergens↗
PubMed1995

Loratadine in the treatment of cough associated with allergic rhinoconjunctivitis.

BACKGROUND: Antihistaminic treatment of allergic asthma or cough-type asthma, including cough associated with allergic rhinocojunctivitis, has been recently reconsidered prospectively since new very potent compounds, nonsedating with anti-allergic properties, are available. OBJECTIVE: The possible effectiveness of loratadine in the treatment of allergic cough was assessed in 20 patients with allergic rhinoconjunctivitis and cough due to Parietaria judaica during the pollen season (April to July 1993). METHODS: Allergic patients were enrolled in a double-blind, placebo-controlled, parallel-group, randomized study, and received loratadine 10 mg/d or placebo in oral tablets for 4 weeks. Occurrence and severity of conjunctival and nasal symptoms, severity and frequency of cough attacks were assessed daily by the patients together with peak expiratory flow evaluation performed twice a day, ie, in the morning and in the evening. Physicians evaluated conjunctival and nasal signs, and spirometry on admission (before treatment), 2 and 4 weeks after treatment. On admission methacholine challenge was also performed to assess PD20. Pollen counts were assessed during the study. RESULTS: According to patients' diary cards, ocular and nasal symptoms were progressively reduced by loratadine treatment (respectively P < .05 and P < .01), as well as cough frequency (P < .05) and cough intensity (P < .01). Peak expiratory flow rate, forced vital capacity, and forced expiratory volume in one second significantly decreased in the placebo-treated group (P < .01), while they were not modified in loratadine-treated patients, who remained normal. CONCLUSIONS: The study suggests that loratadine may be beneficial in the treatment of allergic cough, as well as in rhinoconjunctivitis. Further studies of this may be warranted.

Adult↗
PubMed1994

Evidence of intercellular adhesion molecule-1 expression on nasal epithelial cells in acute rhinoconjunctivitis caused by pollen exposure.

Rhinoconjunctivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during pollen season. It has been recently demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during inflammatory response consequent to allergic reactions. The aim of this study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1 or CD54) on nasal epithelial cells, before and during natural seasonal exposure, in 10 allergic patients (Parietaria judaica-sensitized) and in 10 healthy volunteers, correlating this parameter with clinical and cytologic involvement. Nasal epithelial cells of allergic subjects showed a significant expression of CD54 during pollen season (p < 0.001). On the contrary, no CD54 expression was observed out of pollen season. In healthy volunteers no CD54 expression was observed both before and during pollen season. Cytologic evaluation demonstrated an infiltration by eosinophils (mainly activated [EG2+]), (p < 0.001), neutrophils (p < 0.001), and metachromatic cells (p < 0.001) during pollen season only in allergic subjects. Therefore results indicate that seasonal allergic rhinitis is characterized by an infiltration of inflammatory cells correlated with CD54 expression on nasal epithelial cells. This phenomenon is specific, being restricted only to allergic patients during pollen season.

Acute Disease↗
PubMed1994

A three-year double-blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric patients.

Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.

Administration, Oral↗
PubMed1994

Effects of conjunctival hyperosmolar challenge in allergic subjects and normal controls.

Nonspecific hyperreactivity to a number of physical, chemical and pharmacological agents in a common characteristics of allergic subjects, which is strictly related to the inflammatory events consequent to an allergic reaction. Hyperosmolar stimulus has previously been shown to cause an inflammatory response inducing mast cell activation and subsequent mediator release. We investigated the clinical and cytological events following conjunctival challenge using a hyperosmolar agent (i.e. glucose solution) in patients with allergy due to pollen, in patients with allergy due to mites and in healthy individuals in order to investigate the possible existence of 'conjunctival hyperreactivity', similar to the well-known nasal and bronchial nonspecific hyperreactivity in allergic patients. Hyperosmolar stimulus was able to produce an immediate inflammatory response evidenced by clinical symptomatology, inflammatory cell infiltrate and CD54 expression on conjunctival epithelium in all allergic subjects and healthy volunteers. House dust mite-sensitive subjects, but not pollen-sensitive subjects studied out of pollen season, showed conjunctival hyperreactivity as shown by histamine challenge, in that they required lower glucose concentrations to elicit the conjunctival reaction. This is probably related to an underlying although mild, inflammation.

Adolescent↗
PubMed1994

Allergen-specific challenge induces intercellular adhesion molecule 1 (ICAM-1 or CD54) on nasal epithelial cells in allergic subjects. Relationships with early and late inflammatory phenomena.

Intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on epithelial cells (EC) has been demonstrated to play a role in the local molecular events of inflammation following allergen-specific conjunctival challenge. In the light of these observations, we evaluated the possible expression of ICAM-1 on nasal EC after allergen-specific challenge. Three groups of subjects were studied: (1) 14 symptomless patients sensitized to mites, (2) 15 symptomless patients sensitized to pollen, and (3) 10 healthy volunteers as controls. The study was performed during winter. At baseline we found that both pollinosic and healthy subjects did not express CD54 on epithelial cells, whereas mite-sensitive patients showed a mild expression (possibly caused by a persistent natural allergen exposure). In addition, clinical and cellular responses were induced by lower allergen dosages in mite-sensitive patients compared with pollen-sensitive patients. CD54 was detectable in all the allergic patients but not in the control subjects 30 min after challenge. At 6 h all patients showed a marked inflammatory infiltration and CD54 persistence on EC: such an infiltration was more relevant in patients developing clinical late-phase reaction (LPR). Finally, 24 h after challenge EC CD54 expression persisted, as well as a cellular infiltrate mainly caused by eosinophils (the latter being more pronounced in mite-sensitive individuals). CD54 should be regarded as an early and sensitive marker of inflammation in both LPR-positive and LPR-negative patients. A cellular inflammatory infiltrate was detectable in both LPR-positive and LPR-negative subjects, although relevant differences in eosinophil counts were observed between the two groups. The study emphasizes the importance of the different events of inflammation in allergy.

Adolescent↗
PubMed1993

Protective effects of deflazacort on allergen-specific conjunctival challenge.

The protective effects of deflazacort, (a new heterocyclic glucocorticoid and derivative of prednisolone, with calcium and glucose-sparing effects) on the inflammatory reaction following an allergen-specific conjunctival provocation test (CPT) were assessed in a double-blind study, in 24 patients suffering from rhinoconjunctivitis due to Parietaria judaica. After an initial screening CPT, patients were randomized to four treatment groups, to receive deflazacort, 6, 30 or 60 mg, once daily or placebo, for 3 days, during the low-pollen season. Clinical evaluations (itching, hyperaemia, lacrimation and eyelid swelling), cytological assessment (number of inflammatory cells, i.e. neutrophils, eosinophils and lymphocytes, sampled by conjunctival scraping) and immunocytochemical evaluation of CD54 (intercellular adhesion molecular-1 [ICAM-1]) expression on epithelial cells were performed after CPT, at baseline, after 30 minutes (early-phase reaction [EPR]) and after 6 and 24 hours (late-phase reaction [LPR]), before and after treatment. Neither the nature or severity of clinical events nor the total number of inflammatory cells during the EPR changed during treatment with deflazacort. The severity of the clinical events during the LPR were significantly reduced by deflazacort, 30 and 60 mg/day P < 0.01) compared to the placebo-treated group. The total number of inflammatory cells during the LPR was also significantly reduced by deflazacort, 30 and 60 mg/day (P < 0.01) compared to the placebo-treated group. CD54 expression was significantly reduced by deflazacort, 30 and 60 mg/day both during the EPR (P < 0.01) and LPR (P < 0.01) compared to the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗