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Biomedical subjects

F Bonifazi

Publications and source records attributed to F Bonifazi.

At least 19 recordsLinked to original sources
PubMed2006

Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years.

OBJECTIVE: The 1995-2005 balance of EMEA activities in the field of paediatric medicines was evaluated, taking into account the number both of drugs authorised for children and paediatric studies supporting the Marketing Authorisation (MA). METHODS: Data on drugs authorised by EMEA were extracted from EPARs (European Public Assessment Reports). Active substance, year of approval, anatomical, therapeutic and chemical (ATC) code, indication, orphan status, ages, and registrative clinical studies characteristics were assessed. RESULTS: The percentage of authorised substances for paediatrics is 33.3%. This percentage decreased or increased when different subsets of medicines were considered [medicines for children under 2 years (23.4%), N-ATC code drugs (6%) and orphan drugs (46.4%)]. A total of 165 trials were included in the MA dossiers of 51 drugs at the time of approval, and additional 22 studies were added to the dossiers of 12 active substances submitted for paediatric variations. PK and Efficacy/Safety studies were performed for 32 (52%) active substances, while either one PK or one Efficacy/Safety study was carried out for 43 (69%) and 45 (73%) substances, respectively. CONCLUSIONS: This report demonstrates that the total number of paediatric medicines approved by EMEA is stable over the 10-year period, while an increase in drugs to treat serious or orphan diseases has been observed. In addition, under the Centralised Procedure, a valuable number of paediatric trials have been submitted to support drug approval.

Adolescent↗
PubMed2006

European Polistes venom allergy.

The American Polistes species venom mixture--that of P. annularis, P. fuscatus, P. metricus and P. exclamans--was the only commercially available mixture for diagnosis and therapy until 1996. However, these species of Polistes are not present in Europe, where P. dominulus and P. gallicus and to a lesser extent P. nimphus are widespread. The aim of this study was to assess the allergenic differences among the commercial American mix, P. dominulus and P. gallicus venom in European patients and therefore to verify if this mixture is suitable for diagnosis in these patients. We carried out skin tests, radioallergosorbent tests (RAST) and RAST inhibition in Italian patients with adverse reactions to Polistes stings. RAST inhibition results demonstrated that cross-reactivity between the American and European species is only partial and that P. dominulus and P. gallicus venoms have exclusive allergens. Skin tests and direct RAST confirmed these results and also showed that European Polistes venom is more suitable than the American mix in Italian patients. Moreover, we found a high rate of cross-reactivity between P. dominulus and P. gallicus. To conclude, P. dominulus and/or P. gallicus venoms are necessary for diagnosis and therefore in the therapy of European patients.

Adolescent↗
PubMed2005

Short- and long-term haematological surveillance of healthy donors of allogeneic peripheral haematopoietic progenitors mobilized with G-CSF: a single institution prospective study.

Healthy allogeneic donors, who were treated with G-CSF and underwent peripheral blood haematopoietic precursor collection at our Institution, were enrolled in a short- and long-term haematological surveillance protocol for a 5--7--year period. To date, 94 donors have been assessed with a mean follow-up of 30 months (4--84); for 30 subjects, the follow-up is >or=48 months. During G-CSF administration, 23/94 donors showed a significant platelet count decrease from the baseline. Pre-apheresis platelet decrement correlated with the total G-CSF dose administered, baseline platelet level and donor age. Normal platelet counts returned within 4--8 months. PMN and/or lymphocyte lower values were observed in 55/94 donors 2 weeks after G-CSF administration, with mean drops from the baseline of 40 and 36% for PMN and lymphocytes, respectively. The PMN decrease correlated inversely with donor age, as younger donors were more affected than older ones, whereas the lymphocyte decrease correlated directly with the total blood volumes processed in the apheresis courses, in particular for donors subjected to large volume leukaphereses. Long-term observation showed moderate neutrophil reduction (25% count drop from the baseline) in four of the 30 donors observed for four years or more. 14 donors showed persistent, slight lymphocytopenia (mean drop of 13%) until the third year, with recovery in the fourth year of follow-up.

Adult↗
PubMed2005

The autologous serum skin test in the follow-up of patients with chronic urticaria.

BACKGROUND: The presence of anti-FcepsilonRI and anti-IgE autoantibodies in a subset of patients with chronic urticaria suggests their aetiopathogenetic role. In clinical practice, the presence of these antibodies is usually considered when the autologous serum skin test (ASST) is positive. AIMS: To evaluate if the positive ASST follows up the activity of chronic urticaria. METHODS: Autologous serum skin test and thyroid autoantibody detection were performed in 82 patients with chronic urticaria and repeated 1 year later, when the vast majority of patients were symptom-free. Twenty patients with Hashimoto thyroiditis (HT), who had never suffered from urticaria, represented the control group. RESULTS: At the start of the study, the prevalence of positive ASST was 46.6%. The association of HT-urticaria was 29.3%. ASST was positive in 62 and 39% of patients with and without HT, respectively (P > 0.05 ns). One year later, 28 of 34 patients with a positive ASST were symptom-free, but 50% of them were positive for ASST. The ASST was positive in 86.7 and 8% of patients with and without HT, respectively (P < 0.001). In the control group, ASST was always negative. CONCLUSIONS: The co-existence of autoimmune thyroiditis with chronic urticaria seems to induce a significant difference in the persistence of a positive ASST. Consistent with previous reports, a positive ASST correlates with disease exacerbation in chronic urticaria patients without thyroiditis. In patients with thyroiditis and urticaria, positive ASST persists even after the urticaria has disappeared, thus questioning whether a positive ASST to be a surrogate marker of the functional role of anti-FcepsilonRI and anti-IgE autoantibodies.

Adult↗
PubMed2005

Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice.

Based on the knowledge of the living conditions and habitat of social Aculeatae a series of recommendations have been formulated which can potentially greatly minimize the risk of field re-sting. After a systemic sting reaction, patients should be referred to an allergy specialist for evaluation of their allergy, and if necessary venom immunotherapy (VIT). An emergency medical kit should be supplied, its use clearly demonstrated and repeatedly practised until perfected. This should be done under the supervision of a doctor or a trained nurse. Epinephrine by intramuscular injection is regarded as the treatment of choice for acute anaphylaxis. H1-antihistamines alone or in combination with corticosteroids may be effective in mild to moderate reactions confined to the skin and may support the value of treatment with epinephrine in full-blown anaphylaxis. Up to 75% of the patients with a history of systemic anaphylactic sting reaction develop systemic symptoms once again when re-stung. Venom immunotherapy is a highly effective treatment for individuals with a history of systemic reaction and who have specific IgE to venom allergens. The efficacy of VIT in yellow jacket venom allergic patients has been demonstrated also by assessing health-related quality of life. If both skin tests and serum venom specific IgE turn negative, VIT may be stopped after 3 years. After VIT lasting 3-5 years, most patients with mild to moderate anaphylactic symptoms remain protected following discontinuation of VIT even with positive skin tests. Longer term or lifelong treatment should be considered in high-risk patients. Because of the small but relevant risk of re-sting reactions, in these patients, emergency kits, including epinephrine auto-injectors, should be discussed with every patient when stopping VIT.

Adult↗
PubMed2005

Diagnosis of Hymenoptera venom allergy.

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.

Allergens↗
PubMed2005

Intraoperative anaphylaxis: verba volant, scripta manent!

We describe a case of intraoperative gelatine-induced anaphylaxis whose diagnosis was delayed as the use of gelatine during surgical procedures was omitted for two times in patient's medical records. The subject is a 66-year old woman, with a negative medical history of atopy, food and drug allergy, with arterial hypertension on a course of beta-blockers and with bladder carcinoma requiring surgery. The patient had tolerated both general and local anaesthesia on several previous occasions. On the first occasion she experienced arterial fibrillation secondary to a severe episode of hypotension following local anaesthesia, while on a course of beta-blockers. On the second occasion she developed a very severe episode of hypotension followed by the outbreak of a generalised rash during general anaesthesia. The tryptase sera level was 109 mg/L one hour after the reaction had subsided, while the basal values were normal. On the third occasion the patient redeveloped severe hypotension and a generalised rash during general anaesthesia. The allergological work-up was negative, except for intradermal test with gelatine. A study of the intra-cellular cytokines in blood lymphocytes showed a production of IL4 from CD4+ lymphocytes after stimulation by gelatine. The patient underwent a successive surgical procedure without any adverse event.

Adrenergic beta-Antagonists↗
PubMed2005

The dilemma of the negative skin test reactors with a history of venom anaphylaxis: will this always be the case?

The loss of sensitization over time, the involvement of a different pathogenetic mechanism and the poor sensitivity of diagnostic tests have been included among the causes of a non IgE-mediated anaphylaxis triggered by an insect sting. To provide further insight into this topic we describe the case of a patient suffering from urticaria pigmentosa, anaphylactic shock due to a Vespid sting and monosensitive to Polistes dominulus venom, who was previous diagnosed with non-IgE mediated insect sting anaphylaxis in subjects with urticaria pigmentosa. Therefore ultra-rush specific immunotherapy using an acqueous Polistes dominulus venom extract was performed over two mornings until a total dose of 100mcg was reached without any side effects. Presently the patient is undergoing maintenance therapy with a depot Polistes dominulus venom extract at 4-weekly intervals and is free of side effects. In conclusion, despite the high cross-reactivity among the venoms of the various species of Polistes, recent evidence of a selective specificity unique to European Polistes allergens raises the problem of the need to make the American Polistes venom as well as that of Polistes dominulus (a very common insect in Europe) available both for diagnostic and therapeutic purposes. Besides the fact that the presence of urticaria pigmentosa alone could have explained the anaphylactic reaction to the aspecific stimulation triggered by the venom, this case history also demonstrates that omitting to perform skin tests for Polistes dominulus venom would have led to the same misdiagnosis of non IgE-mediated anaphylaxis and served only to further delay commencing specific immunotherapy.

Adult↗
PubMed2004

Busulfan neurotoxicity and EEG abnormalities: a case report.

A 21-year-old woman with acute lymphoblastic leukemia underwent bone marrow transplantation (BMT). The conditioning regimen consisted of an association of busulfan (BU) and cyclophosphamide (Cy). The day after starting BU, she suffered a generalized tonic-clonic seizure. Electroencephalography (EEG) performed the day after the seizure showed diffuse polyspikes and spike-and-wave discharges. EEG on the following days showed persistent abnormalities (slowing of background activity intermixed with diffuse slow waves and isolated delta and theta bursts). These abnormalities persisted for about 20 days with complete normalization one month after the seizure. We suggest that BU is implicated in these abnormalities and emphasize the importance of EEG recording before and after bone marrow transplantation to disclose BU neurotoxicity.

Acute Disease↗
PubMed2004

Contemporaneous appearance, 18 years after allogeneic bone marrow transplantation, of myelodysplastic syndrome in the patient and the donor.

We report the case of the development of two different stages of the same clonal disorder in two patients sharing the same bone marrow due to a previous bone marrow allotransplant. The transplanted patient developed severe aplasia with myeloid blasts, different from those of the previously cured leukemia. Chimerism evaluated by microsatellite analyses confirmed a full donor phenotype. At the same time, the donor of the bone marrow transplantation developed a refractory anemia with excess blasts. We speculate on the presence of an undetectable pre-existing pathological clone in the transplanted bone marrow, which have evolved in the two patients.

Adult↗
PubMed2004

Asthma severity and medical resource utilisation.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1-November 30, 1999, and 500 consecutive patients with asthma, aged 18-55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros (Euros) for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be Euros 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to Euros 720, Euros 1,046, Euros 1,535 and Euros 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.

Activities of Daily Living↗