RESUMO
BACKGROUND: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. AIM: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. METHOD: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. RESULTS: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). CONCLUSIONS: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately.
Assuntos
Asma/terapia , Padrões de Prática Médica/estatística & dados numéricos , Qualidade de Vida , Especialização , Adulto , Idoso , Asma/fisiopatologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Inhibition of multiple myeloma (MM) plasma cells in their permissive bone marrow microenvironment represents an attractive strategy for blocking the tumor/vessel growth associated with the disease progression. However, target specificity is an essential aim of this approach. Here, we identified platelet-derived growth factor (PDGF)-receptor beta (PDGFRbeta) and pp60c-Src as shared constitutively activated tyrosine-kinases (TKs) in plasma cells and endothelial cells (ECs) isolated from MM patients (MMECs). Our cellular and molecular dissection showed that the PDGF-BB/PDGFRbeta kinase axis promoted MM tumor growth and vessel sprouting by activating ERK1/2, AKT, and the transcription of MMEC-released proangiogenic factors, such as vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). Interestingly, pp60c-Src TK-activity was selectively induced by VEGF in MM tumor and ECs, and the use of small-interfering (si)RNAs validated pp60c-Src as a key signaling effector of VEGF loop required for MMEC survival, migration, and angiogenesis. We also assessed the antitumor/vessel activity of dasatinib, a novel orally bioactive PDGFRbeta/Src TK-inhibitor that significantly delayed MM tumor growth and angiogenesis in vivo, showing a synergistic cytotoxicity with conventional and novel antimyeloma drugs (ie, melphalan, prednisone, bor-tezomib, and thalidomide). Overall data highlight the biologic and therapeutic relevance of the combined targeting of PDGFRbeta/c-Src TKs in MM, providing a framework for future clinical trials.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Mieloma Múltiplo/tratamento farmacológico , Pirimidinas/farmacologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Tiazóis/farmacologia , Quinases da Família src/fisiologia , Adulto , Idoso , Animais , Antineoplásicos , Dasatinibe , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Mieloma Múltiplo/enzimologia , Mieloma Múltiplo/etiologia , Inibidores de Proteínas Quinases , Pirimidinas/uso terapêutico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Tiazóis/uso terapêutico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/antagonistas & inibidoresRESUMO
Aseptic meningitis is a rare but well-recognized complication of drug therapy. The clinical presentation of drug-induced aseptic meningitis (DIAM) is distinct. Symptoms typically include fever, neck stiffness, headache, confusion, nausea and vomiting. The major categories of causative agents are non-steroidal anti-inflammatory drugs, antimicrobials and also intravenous immunoglobulins, monoclonal antibodies and vaccines. These drugs most commonly implicated as causes of aseptic meningitis act more likely through an immunological mechanisms. However, the exact pathogenetic mechanism of DIAM is still unknown. The diagnosis of drug-induced aseptic meningitis is difficult and infectious etiologies must be excluded. In some cases the diagnosis has been confirmed by rechallenging the patient with the suspected agent. In this case, informed written consent is necessary and rechallenge must be medically supervised both to document the response and to offer medical care and advice, if required. The outcome of DIAM is generally good, usually without long term sequelae.
Assuntos
Meningite Asséptica/induzido quimicamente , Adjuvantes Imunológicos/efeitos adversos , Animais , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Meningite Asséptica/diagnóstico , Meningite Asséptica/imunologia , Vacinas/efeitos adversosRESUMO
OBJECTIVE: The purpose of this study was to alert doctors of dental surgery to the possibility of latex sensitivity in both outpatients and inpatients. STUDY DESIGN: The study involved 2 groups: group A was composed of 21 subjects with a history of immediate reaction in dental environment; group B was composed of 24 healthy individuals. Patients underwent skin prick tests with common inhalant allergens, with latex cross-reacting foods, with a commercial extract of non-ammoniated latex, and the incremental challenge test with local anesthetics. Specific IgE to latex and to latex cross-reacting foods were measured with the fluorescent enzyme immunoassay. RESULTS: All patients in group A and none in group B were latex-allergic. Subjects who were latex-allergic were significantly more likely to be atopic and had positive IgE test to cross-reactive foods. CONCLUSIONS: Dentists and people working in a dental surgery environment must obtain detailed patient history to help identify individuals at risk of latex allergy or those actually allergic to latex. If an allergy exists, equipment used should be made of alternative materials.
Assuntos
Equipamentos Odontológicos/efeitos adversos , Hipersensibilidade ao Látex/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Reações Cruzadas , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/etiologia , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/etiologia , Imunoglobulina E/imunologia , Hipersensibilidade ao Látex/diagnóstico , Masculino , Anamnese , Pessoa de Meia-Idade , Teste de Radioalergoadsorção , Testes CutâneosRESUMO
BACKGROUND: Parecoxib is the first injectable cyclooxygenase 2 selective inhibitor indicated for the treatment of acute postoperative pain. OBJECTIVE: To describe the results of a challenge with parecoxib in patients with a history of urticaria or angioedema to 1 or more nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: The study was performed from October 1, 2006, through March 31, 2007, with 79 patients who historically had experienced urticaria or angioedema after use of NSAIDs. The patients underwent a single-blind challenge with parecoxib, 40 mg. RESULTS: No reaction to placebo was observed in any patient. Similarly, no reaction to parecoxib was observed in any patients in the single-class or multiple-class intolerance group. CONCLUSION: Our report demonstrates that parecoxib does not induce cross-reactivity in patients with a history of urticaria or angioedema. Hence, this finding suggests that this drug could be safely proposed as an alternative (but only after a prior challenge) in patients with previous hypersensitive reactions to NSAIDs, even if there are added risk factors such as atopy and antimicrobial allergy, who require an analgesic drug perioperatively.
Assuntos
Angioedema/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Hipersensibilidade a Drogas/imunologia , Isoxazóis/imunologia , Urticária/imunologia , Adolescente , Adulto , Idoso , Angioedema/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Reações Cruzadas/imunologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/imunologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Humanos , Isoxazóis/efeitos adversos , Isoxazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento , Urticária/induzido quimicamenteRESUMO
BACKGROUND: Rofecoxib is a selective cyclooxygenase 2 (COX-2) inhibitor and is well tolerated as an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with a previous adverse reaction to other classes of NSAIDs. Until now, there has not been information in the literature about its long-term tolerability. OBJECTIVE: To provide follow-up data on patients with a history of adverse cutaneous reactions to NSAIDs who underwent and tolerated a challenge test with rofecoxib. METHODS: Study patients had historically experienced cutaneous adverse reactions to aspirin and NSAIDs and had undergone single-blind challenges with rofecoxib, 25 mg. A questionnaire was distributed to all participants. In particular, they were asked to clarify any reactive symptoms they had developed after ingestion of the drug. All patients were reexamined 1 to 3 years after testing. At reexamination, they were carefully and personally interviewed using the previously distributed questionnaire. RESULTS: Of the 182 patients who participated in the study, none reacted to rofecoxib during single-blind challenges. Fifty-one (28%) never received rofecoxib again, whereas 131 (72%) were exposed to rofecoxib, often on multiple occasions. Only 7 (5%) of the 131 patients reported cutaneous reactions to rofecoxib during the 3 years of follow-up. CONCLUSIONS: Rofecoxib appears to be a safe alternative drug among atopic individuals, antibiotic-hypersensitive individuals, and individuals who experienced adverse cutaneous reactions to more than 1 class of NSAIDs, but it is less safe among chronic urticaria patients. Further investigations that include a larger sample are required to confirm our results especially among chronic urticaria patients.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Asma/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Lactonas/efeitos adversos , Sulfonas/efeitos adversos , Adulto , Idoso , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Seguimentos , Humanos , Entrevistas como Assunto , Lactonas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Método Simples-Cego , Sulfonas/uso terapêutico , Urticária/induzido quimicamenteRESUMO
BACKGROUND: Etoricoxib is a novel cyclooxygenase 2 selective inhibitor. Until now, there has not been information in the literature about its tolerability in patients with a history of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To determine the short-term tolerability of etoricoxib in patients with a history of cutaneous adverse reactions to NSAIDs. METHODS: Single-blind challenge testing was performed on 2 different days using placebo (talc) and etoricoxib. On the first day, 2 placebo capsules were administered 1 hour apart; 7 days later, each patient received divided doses of the total therapeutic dose of 90 mg of etoricoxib: 22.5 mg initially and 67.5 mg 1 hour later if no reactive symptoms were noted. RESULTS: Of 141 patients who underwent challenge testing with etoricoxib, only 2 (1.4%) had positive test results; both developed wheals on the extremities. These 2 patients were treated with chlorpheniramine maleate (10 mg intravenously), and the symptoms completely resolved within 2 hours. None of the patients experienced adverse reactions to the placebo challenge. CONCLUSION: The low rate of adverse reactions to etoricoxib, tested by oral challenge, suggests that patients with previous cutaneous hypersensitivity reactions to NSAIDs (primarily urticaria and angioedema) may tolerate this drug.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Toxidermias/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Piridinas/efeitos adversos , Sulfonas/efeitos adversos , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/imunologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/imunologia , Demografia , Toxidermias/imunologia , Hipersensibilidade a Drogas/imunologia , Etoricoxib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes , Piridinas/administração & dosagem , Piridinas/imunologia , Método Simples-Cego , Sulfonas/administração & dosagem , Sulfonas/imunologiaRESUMO
Contact dermatitis is the most frequent occupational dermatosis and non-specific irritants in addition to specific Type IV sensitization are involved. We reviewed our database for data from 1994 to 1998 and selected 360 consecutive patients working in healthcare environments and experiencing contact dermatitis at their hands, wrists and forearms. We found that allergic contact dermatitis and irritant contact dermatitis were considered to be work-related in 16.5% (72/436) and 44.4% (194/436) of diagnoses, respectively. Occupational irritant contact dermatitis is due to exposure to a wide range of irritants in the workplace, such as soaps, solvents, cleansers and protective gloves, which conspire to remove the surface lipid layer and/or produce cellular damage. In this study the major relevant aetiological agents that induced occupational allergic contact dermatitis were: nickel sulphate (41 patch positivities), components of disinfectants [glutaraldehyde (5) and benzalkonium chloride (7)] and rubber chemicals [thiuram mix (15), carba mix (9) and tetramethylthiuram monosulphide (6)]. The best treatment for allergic contact dermatitis is to avoid those allergens causing the rash. Whenever this is not possible, contact with them needs to be reduced using properly selected protective gloves. Finally, subjects with atopic dermatitis should avoid 'wet work' and contact with irritants, because atopic dermatitis is significantly associated with irritant contact dermatitis.
Assuntos
Dermatite Alérgica de Contato/etiologia , Dermatite Irritante/etiologia , Dermatite Ocupacional/etiologia , Pessoal de Saúde , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Estudos RetrospectivosRESUMO
The value of recommending latex allergy screening in allergy departments of the Army's Hospital was studied. The purpose of the study was to evaluate whether atopy was a risk factor for latex sensitization in a specific population such as the young male soldiers of the Italian Army. The study was also aimed to assess the role of other risk factors. One thousand five hundred male subjects (1000 subjects who were atopic and 500 subjects who were nonatopic), visiting the Department of Allergology and Respiratory Physiopathology of the Army's Hospital in Bari, Italy, were enrolled into the study. The protocol included a questionnaire (symptoms of atopy, use of latex gloves and condoms and possible reactions previous surgical procedures), a clinical examination, a skin-prick test to latex and common allergens to evaluate atopy, and in part a latex challenge. Among the 1000 subjects who were atopic, 2.8% had evidence for sensitization to latex compared with 1.2% in the 500 subjects in the nonatopic group. The risk of latex sensitization was 19 times higher for subjects with a history of reactions to latex exposure and had a twofold increase for each surgical procedure and for each skin test positivity for inhalant allergens. Another risk factor was positivity to skin-prick tests for Artemisia vulgaris, cypress, and molds. Atopy significantly relates to an increased risk of latex sensitization. Screening is recommended in the Army's Hospital to identify latex-sensitized subjects and inform them about the risks connected with this condition.