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Alberto Tedeschi

Publications and source records attributed to Alberto Tedeschi.

15 recordsLinked to original sources
PubMed2007

Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria.

BACKGROUND: In patients with chronic urticaria (CU), plasma shows signs of thrombin generation and autologous plasma skin tests score positive in as many as 95% of cases. OBJECTIVE: To evaluate the initiators of blood coagulation that lead to thrombin generation and fibrinolysis in CU. METHODS: Activated factor VII, activated factor XII, fragment F(1+2), and D-dimer plasma levels were measured in 37 patients with CU and 37 controls. Skin specimens from 10 patients with CU and 10 controls were tested for tissue factor immunohistochemically. RESULTS: Mean F(1+2) levels were higher in patients than controls (2.54 [SD 2.57] nmol/L vs 0.87 [0.26] nmol/L; P < .001); disease activity was moderate or severe in 9 of 11 (82%) and 9 of 26 (35%) patients showing high or normal F(1+2) levels, respectively (P < .025). Mean D-dimer plasma levels were higher in patients than controls (329 [188] ng/mL vs 236 [81] ng/mL; P < .01); disease activity was moderate or severe in 6 of 8 (75%) and 11 of 29 (38%) showing elevated or normal plasma D-dimer levels (P = NS). Factor VIIa levels were higher in patients than controls (2.86 ng/mL [0.66] vs 1.97 ng/mL [0.65]; P < .001). Activated factor VII and F(1+2) levels were correlated (r = 0.529; P = .008). Tissue factor reactivity was observed only in CU skin specimens. CONCLUSION: The extrinsic pathway of clotting cascade is activated in CU. Disease severity is associated with the activation of the coagulation cascade. CLINICAL IMPLICATIONS: The involvement of the coagulation pathway in CU opens new perspectives for a better understanding of the pathogenesis and, possibly, for the treatment of this disease.

Adolescent↗
PubMed2006

Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum.

BACKGROUND: Several aspects of the pathogenesis of chronic urticaria (CU) remain contradictory. Autologous serum skin tests (ASSTs) and in vitro histamine release assays seem to look into distinct aspects of the disease, and the specificity of ASST has been questioned. OBJECTIVE: We compared the autologous plasma skin test (APST) with ASST to detect autoreactivity in patients with CU. The clotting process was investigated as well by measuring in vivo thrombin generation. METHODS: A total of 96 adults with CU underwent ASST; 71 of them underwent APST with Na citrate-anticoagulated plasma. Prothrombin fragment 1+2 plasma levels were measured by a sandwich ELISA in Na citrate-anticoagulated plasmas from 28 patients and 27 controls. RESULTS: Fifty-one of 96 (53%) patients scored positive on ASST, whereas 61 of 71 (86%) patients scored positive on APST (21/30 [70%] ASST-negative and 40/41 [98%] ASST-positive). Plasma prothrombin fragment 1+2 was higher in patients than controls (3.06 [SD 3.36] vs 0.80 [0.34]; P < .001) and in ASST-positive/APST-positive than in ASST-negative/APST-positive patients (3.89 [SD 3.68] vs 1.33 [1.64]; P = 0.058) and was directly related to urticaria severity (r = 0.37; P < .05). CONCLUSION: Most patients with CU are positive on APST-Na citrate. CU is associated with the generation of thrombin, a serine protease able to activate mast cells and to cause relevant increase in permeability of endothelium. APST and ASST only partially depend on the presence of circulating antibodies to FcepsilonRI or to IgE. CLINICAL IMPLICATIONS: These findings provide new insights into the pathogenesis of CU and suggest new therapeutic opportunities for treating this disease.

Adolescent↗
PubMed2006

Is affluence a risk factor for bronchial asthma and type 1 diabetes?

In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (r(sp): 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (r(sp): 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (r(sp): -0.66, p < 0.0001 for type 1 diabetes; r(sp):- 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (r(sp): -0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (r(sp): -0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes.

Adolescent↗
PubMed2006

Emerging drugs for chronic urticaria.

Chronic urticaria (CU), with or without angioedema, is a frequent disorder defined as the occurrence of pruritic wheals for > 6 weeks. Studies carried out in the last two decades showed that the origin of the disease is autoimmune in up to 50% of cases. Currently available treatments include antihistamines, corticosteroids and ciclosporin; recently, leukotriene receptor antagonists proved effective in a subset of patients as well. For patients with an unremitting and extremely severe disease unresponsive to standard treatments, plasmapheresis and immunosuppressive drugs have been successfully attempted. Recent findings that the autologous plasma skin test scores positive in nearly all patients and that plasmas from patients with both autoimmune and 'idiopathic' chronic urticaria are frequently characterised by signs of thrombin activation (plasma levels of prothrombin fragment F(1.2) are significantly increased) suggest that clotting cascade might be somehow involved in the pathogenesis of CU. These findings put under a new light some rather sparse studies of the effect of drugs active on the coagulation system (heparin and oral anticoagulants) in patients with CU.

Chronic Disease↗
PubMed2006

Diagnosis of latex hypersensitivity: comparison of different methods.

A standardized diagnostic protocol for latex allergy is still lacking, although latex-related manifestations are a common health problem especially among health-care workers and patients with spina bifida. The present study was aimed to compare different in vivo (skin prick test, patch test, use test) and in vitro (specific IgE determination by CAP-Rast, basophil histamine release assay, immunoblot) methods to diagnose latex sensitization in 47 health care workers reporting latex-related manifestations. According to the established criteria, 20 subjects (42.5%) were considered as truly sensitized to latex, 18 with type I and 2 with type IV hypersensitivity. Skin prick test displayed the highest diagnostic efficiency, having higher sensitivity and specificity than specific IgE determination and use test. Patch test with rubber chemicals had a low sensitivity, but a good specificity. Basophil histamine release and immunoblot showed low sensitivity and specificity. A combination of clinical history and skin prick test should be used in order to diagnose latex allergy, except in those subjects reporting life-threatening reactions, in which in vitro specific IgE determination must be preferred. Patch testing with rubber chemicals should be reserved to selected cases. Basophil histamine release and immunoblotting can be performed for research purpose, but cannot be recommended for routine diagnostic use.

Adult↗
PubMed2004

Role of sodium in intracellular calcium elevation and leukotriene B4 formation by receptor-mediated activation of human neutrophils.

The role of Na(+) and Na(+) exchangers in intracellular Ca(2+) elevation and leukotriene B(4) (LTBs) formation was investigated in granulocyte macrophage colony-stimulating factor (GM-CSF)-primed, fMLP-stimulated human neutrophils. Isotonic substitution of extracellular Na(+) with N-methyl-D-glucamine(+) (NMDG(+)) resulted in over 85% inhibition of the LTBs generation observed (from 14.1+/-0.9pmol/10(6) neutrophils to 1.7+/-1.0pmol/10(6) neutrophils at 0.3 microM fMLP). Isotonic substitution of Na(+) with NMDG(+) also induced a significant inhibition of fMLP-induced rise in cytosolic Ca(2+) concentration ([Ca(2+)](i)) (from 2.17- to 0.78-fold increase over basal levels). Pretreatment with an inhibitor of the Na(+)/Ca(2+) exchanger (benzamil) did not inhibit either [Ca(2+)](i) rise or LTBs production, indicating that the observed effects of extracellular Na(+)-deprivation were unrelated to the Na(+)/Ca(2+) exchanger in receptor-mediated Ca(2+) influx, as previously hypothesized. LTBs production by thapsigargin-activated neutrophils was not affected by Na(+) depletion, but was totally abolished in the presence of EGTA, suggesting that store depletion-driven extracellular Ca(2+) influx is required for leukotriene synthesis and that this process is independent of Na(+)-deprivation. Exposure to Na(+)-free medium for the time of GM-CSF priming led to a significant decrease of intracellular pH values, suggesting a role of the Na(+)/H(+) exchanger in intracellular Na(+) depletion. Reducing the time of Na(+)-deprivation totally reversed the observed effect on LTBs production, resulting in enhanced, rather than inhibited, formation of LTBs. These results indicate that LTBs generation and [Ca(2+)](i) rise in human neutrophils primed by GM-CSF and stimulated with fMLP is dependent on intracellular Na(+) concentration, and, at variance with previously published results, unrelated to the Ca(2+) influx through the Na(+)/Ca(2+) exchanger.

Biological Transport↗
PubMed2003

Circulating stem cell factor in patients with chronic idiopathic urticaria.

BACKGROUND: The nature of histamine-releasing factors involved in the pathogenesis of chronic idiopathic urticaria (CIU) is still controversial, since functional IgG autoantibodies specific for the high-affinity IgE receptor, Fc(epsilon)RI, can be detected in only 20% of patients showing a strong skin reactivity on the autologous serum skin test. The absence of systemic eosinophilia in CIU patients, along with the increase in mast cells in skin biopsy specimens, suggests a possible role for stem cell factor (SCF), the only cytokine/growth factor known to induce mediator release from human mast cells. OBJECTIVE: To investigate the possible role of SCF as a histamine-releasing factor in patients with CIU. METHODS: The SCF levels were measured in serum samples from 65 patients with CIU who scored strongly positive on the autologous serum skin test; of these patients, 32 had negative results and 33 had positive results on in vitro histamine release assay by a quantitative commercial sandwich immunoassay technique. Serum samples from 40 healthy subjects were used as controls. RESULTS: Serum SCF levels in all 65 CIU patients did not differ from those found in healthy controls. No difference in SCF levels was found between patients with positive and negative results on histamine release assay. CONCLUSIONS: An increase in serum SCF levels does not play a pathogenic role in CIU.

Autoantibodies↗
PubMed2003

Sera from patients with multiple drug allergy syndrome contain circulating histamine-releasing factors.

BACKGROUND: A subset of drug-intolerant patients show a marked propensity to react to several chemically unrelated antibacterial drugs. This condition is termed multiple drug allergy syndrome (MDAS). The pathogenesis of MDAS is still unclear. A possible mechanism is that a nonspecific patient-related factor leading to direct histamine release from mast cells and basophils is involved. We investigated whether a patient-related facilitating factor such as the clinically unapparent presence of circulating histamine-releasing factors may represent a nonspecific mechanism underlying drug-induced histamine release in patients with MDAS. METHODS: 38 otherwise healthy adults with a history of acute urticaria following the ingestion of antibacterial drugs [18 subjects with MDAS (patients) and 20 monosensitive subjects (drug-allergic controls) on the basis of both clinical history and single-blind peroral challenges with alternative substances] and 20 subjects without a history of drug allergy (normal controls) underwent an autologous serum skin test (ASST). IgE specific for beta-lactams was measured in sera from 25 subjects (11 patients and 14 drug-allergic controls) with a history of amoxicillin intolerance. Sera from 13 patients and 5 drug-allergic controls (all positive on ASST) were used in the in vitro histamine release assay using basophils from 3 normal donors. RESULTS: 17 of 18 patients (94%) versus 8 of 20 drug-allergic controls (40%) showed an unequivocal wheal-and-flare reaction on ASST (p < 0.05). Skin reactions were generally more intense in the patient group. In one MDAS patient, the ASST was not assessable due to dermographism. No normal control was positive on ASST. Sera from 3 of 13 patients (23%) versus 0 of 6 drug-allergic controls (not significant) induced significant histamine release from basophils of normal donors. IgE specific for beta-lactams was detected in sera from 1 of 11 patients (9%) versus 5 of 14 drug-allergic controls (36%) (not significant). CONCLUSION: Most patients with MDAS and more than one third of subjects with a history of hypersensitivity to a single antibacterial drug were characterized by the presence of circulating histamine-releasing factors. Such factors might play a role in drug-induced adverse reactions observed in these patients.

Adolescent↗
PubMed2003

Chronic urticaria: a role for newer immunomodulatory drugs?

Chronic urticaria is now recognized as an autoreactive disorder in a substantial fraction of patients. A serologic mediator of whealing has been demonstrated in 50-60% of patients with chronic urticaria, and autoantibodies against the high affinity IgE receptor or IgE have been detected in about half of these patients. The demonstration that chronic urticaria is frequently autoimmune has encouraged a more aggressive therapeutic approach, with the use of immunomodulatory drugs.A step-by-step approach to the management of chronic urticaria is proposed, based on our personal experience and review of current medical literature, identified through Medline research and hand searching in medical journals. The non- or low-sedating H(1) receptor antagonists (antihistamines), such as cetirizine, fexofenadine, loratadine, mizolastine and, more recently, levocetirizine, desloratadine and ebastine, represent the basic therapy for all chronic urticaria patients. Older sedating antihistamines, such as hydroxyzine and diphenhydramine, may be indicated if symptoms are severe, are associated with angioedema, and if the patient is anxious and disturbed at night.Corticosteroid therapy with prednisone or methylprednisolone can be administered for a few days (7-14) if urticarial symptoms are not controlled by antihistamines and a rapid clinical response is needed. In cases of relapse after corticosteroid suspension, leukotriene receptor antagonists, such as montelukast and zafirlukast, should be tried. In our experience, remission of urticarial symptoms can be achieved in 20-50% of chronic urticaria patients unresponsive to antihistamines alone. When urticaria is unremitting and is not controlled by combined therapy with antihistamines and leukotriene receptor antagonists, prolonged corticosteroid therapy may be needed. Long-term corticosteroid therapy should be administered at the lowest dose able to control urticarial symptoms, in order to minimize adverse effects. In a few patients, however, high-dose corticosteroid therapy may have to be administered for long periods. In these patients, immunosuppressive treatment with low-dose cyclosporine can be started. This type of treatment has a corticosteroid-sparing effect and is also generally effective in patients with severe, unremitting urticaria, but requires careful monitoring of cyclosporine plasma concentration and possible adverse effects. Other immunomodulating drugs that have been tried in chronic urticaria patients include hydroxychloroquine, dapsone, sulfasalazine and methotrexate, but their efficacy has not been proven in large controlled studies. Warfarin therapy may also be considered in some patients with chronic urticaria and angioedema unresponsive to antihistamines.

Adjuvants, Immunologic↗
PubMed2002

Autoreactivity is highly prevalent in patients with multiple intolerances to NSAIDs.

BACKGROUND: A subset of drug-allergic patients show a marked propensity to react against several, chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenesis of such multiple drug reactions is unclear. Approximately 30% of patients with chronic idiopathic urticaria, a condition frequently characterized by autoreactivity on autologous serum skin test (ASST), experience flares of hives after taking chemically unrelated NSAIDs. OBJECTIVE: To detect whether a clinically unapparent autoreactivity may represent the nonspecific mechanism facilitating drug-induced histamine release in patients with a history of urticaria/angioedema induced by several, chemically unrelated NSAIDs. METHODS: Thirty-six adults with a history of acute NSAID-induced urticaria (22 with multiple NSAID sensitivity [MNS]; 14 with single NSAID sensitivity [SNS]; and 20 atopic controls without a history of drug allergy) underwent ASST. Sera from 14 MNS and 4 SNS subjects (all ASST-positive) underwent histamine release assay with basophils from normal donors. Sera from five MNS patients were tested on autologous basophils as well. RESULTS: Twenty of 22 (91%) MNS subjects versus 5 of 14 (36%) SNS subjects were positive on ASST (P < 0.01). No atopic control was ASST-positive. Sera from 4 of 14 (29%) MNS patients versus 0/4 SNS subjects (P = NS) induced significant histamine release from basophils of normal donors. The use of autologous basophils did not significantly change these results. CONCLUSION: Most patients with multiple NSAID intolerance and approximately one-third of those with single NSAID hypersensitivity are characterized by the presence of circulating histamine-releasing factors. Their nature is still unclear, but the fact that only a minority of sera from ASST+ subjects were able to induce histamine release from normal basophils in vitro suggests that these factors might not differ from those involved in most patients with chronic urticaria. These factors might play a relevant pathogenic role in NSAID-induced urticaria reactions.

Adolescent↗