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1.
BMC Med ; 18(1): 178, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32654663

RESUMO

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).


Assuntos
Anemia Ferropriva/complicações , Compostos Férricos/efeitos adversos , Hipofosfatemia/etiologia , Ferro/sangue , Maltose/análogos & derivados , Adulto , Anemia Ferropriva/sangue , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Maltose/efeitos adversos , Estudos Prospectivos
2.
Clin Exp Immunol ; 194(3): 361-370, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30099753

RESUMO

Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2-6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5-4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Polissacarídeos Bacterianos/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Feminino , Teste de Histocompatibilidade , Humanos , Imunização Secundária , Imunoglobulina G/imunologia , Masculino , Meningite Meningocócica/imunologia , Meningite Meningocócica/microbiologia , Militares , Vacinação , Adulto Jovem
3.
Eur Arch Psychiatry Clin Neurosci ; 268(4): 321-335, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29356899

RESUMO

BACKGROUND: Mindfulness training is a promising treatment approach in adult ADHD. However, there has not yet been a randomized controlled trial comparing mindfulness to an active control condition. In this study, we assessed the efficacy of a mindfulness training program (MAP) compared to structured psychoeducation (PE). METHODS: After randomization 81 medication-free adult ADHD patients participated either in an 8-week MAP or PE group program. At baseline (T1), after 8 weeks (T2) and after 8 months (T3), severity of ADHD and associated symptoms (depression, general psychopathology, quality of life) were measured with the Conner's ADHD Rating Scales (CAARS), the Beck Depression Inventory (BDI), the Brief Symptom Inventory (BSI) and the SF-36 by self and blind observer ratings. RESULTS: Both groups showed significant pre-post improvements in observer-rated Inattention scale (p < .001, partial η2 = 0.18) and in associated symptomatology, which persisted through 6 months of follow-up. There were no significant differences regarding symptom reduction between the treatment groups. Women benefited more compared to men irrespective of treatment group. Men showed the most pronounced changes under MAP. CONCLUSIONS: In the current study, MAP was not superior to PE regarding symptom reduction in adult ADHD. Both interventions, mindfulness meditation and PE, were efficacious in reducing symptom load in adult ADHD. Furthermore in exploratory post hoc tests the study provides evidence for a potential gender-specific treatment response in adult ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/reabilitação , Atenção Plena/métodos , Educação de Pacientes como Assunto/métodos , Resultado do Tratamento , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Autorrelato , Índice de Gravidade de Doença , Caracteres Sexuais
4.
Allergy ; 73(2): 421-430, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28791748

RESUMO

BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years. METHODS: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). RESULTS: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. CONCLUSIONS: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.


Assuntos
Alérgenos/sangue , Alérgenos/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Alemanha , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estudos Prospectivos
5.
Clin Exp Obstet Gynecol ; 43(1): 88-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27048024

RESUMO

PURPOSE OF INVESTIGATION: To evaluate the maternal and neonatal outcomes in twin pregnancies according to chorionicity (monochorionic (MC) versus dichorionic (DC) and type of conception [spontaneously conceived (SC) versus assisted reproduction technology (ART)]. MATERIALS AND METHODS: A retrospective study of 196 twin pregnancies admitted to the Department of Gynecology, Obstetrics and Urology of the University of Rome Sapienza, from January 2008 to April 2013. RESULTS: There were 55 MC and 141 DC twin pregnancies (82 SC and 59 ART). MC twin pregnancies had a higher incidence of preterm birth (p < 0.008), twin-twin transfusion syndrome (TTTS) (p < 0.021), and intrauterine growth restriction (IUGR) (p < 0.05). MC pregnancies had lower neonatal birth weight (p < 0.05), and lower Apgar score. ART DC pregnancies had a higher incidence of preterm delivery (p < 0.05). CONCLUSIONS: MC twin pregnancy is associated with higher risk of adverse maternal and perinatal outcomes. In the DC subgroup, ART is associated to a higher incidence of preterm delivery.


Assuntos
Córion/citologia , Fertilização , Retardo do Crescimento Fetal/diagnóstico , Transfusão Feto-Fetal/diagnóstico , Gravidez de Gêmeos , Adulto , Índice de Apgar , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Estudos Retrospectivos
6.
Q J Nucl Med Mol Imaging ; 58(3): 258-68, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25265247

RESUMO

B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients.


Assuntos
Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/imunologia , Linfócitos B/diagnóstico por imagem , Linfócitos B/imunologia , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Tomografia Computadorizada de Emissão/métodos , Animais , Doenças Autoimunes/patologia , Rastreamento de Células/métodos , Humanos , Inflamação/patologia , Compostos Radiofarmacêuticos/imunologia
7.
Eur J Intern Med ; 25(6): 511-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24877856

RESUMO

Sepsis syndrome is characterized by a systemic inflammatory response to infection potentially leading to acute organ failure and rapid decline to death. Polyclonal intravenous immune globulin, a blood product derived from human donor blood, in addition to antiinfective activities, also exerts a broad antiinflammatory and immunomodulating effect. Intravenous immunoglobulin (IVIg) has been proposed as adjuvant therapy for sepsis even though the clinical studies demonstrating their efficacy and safety are relatively small. Several systematic reviews and meta-analyses of intravenous immunoglobulin treatment in sepsis have been performed. As a result of heterogeneity across studies and inconsistencies in results, the majority have concluded that more evidence, coming from large, well-conducted randomized controlled trials (RCTs), is required. Moreover the appropriate timing of administration and the identification of specific clinical settings represent a key factor to maximizing their beneficial effect. The authors, in this revision, review the basic mechanisms of action of IVIg, the rationale for their use, and their clinical applications.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Choque Séptico/terapia , Humanos , Sepse/terapia , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-24809276

RESUMO

B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasmacells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 Rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients.

9.
Clin Exp Immunol ; 177(3): 630-40, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24773026

RESUMO

The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg ) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti-TNF-α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti-TNF-α failed, are immunologically prone to benefit from an agent targeting a different pathway.


Assuntos
Artrite Reumatoide/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Imunoconjugados/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Abatacepte , Adulto , Idoso , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Humanos , Imunoconjugados/uso terapêutico , Imunofenotipagem , Contagem de Linfócitos , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
10.
Clin Exp Immunol ; 177(1): 287-94, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24666311

RESUMO

Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009-10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Artrite Reumatoide/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , Abatacepte , Adjuvantes Imunológicos/efeitos adversos , Adulto , Antirreumáticos/administração & dosagem , Artrite Reumatoide/complicações , Terapia Biológica , Citocinas/metabolismo , Feminino , Seguimentos , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Itália , Masculino , Pessoa de Meia-Idade , Pandemias , Polissorbatos/efeitos adversos , Estações do Ano , Esqualeno/efeitos adversos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
Eur J Intern Med ; 25(5): 482-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24495663

RESUMO

BACKGROUND: Hepatitis B virus (HBV) reactivation in patients positive for antibody to HB core antigen (anti-HBc), negative for HB surface antigen (HBsAg) and HBV-DNA (potential occult HBV carriers), treated with anti-tumor necrosis factor (TNF)α, is a debated question. The aim of the study was to evaluate the safety of anti-TNFα therapy in anti-HBc positive/HBsAg negative subjects with rheumatoid arthritis (RA) and spondyloarthropathy (SpA). METHODS: All consecutive HBsAg negative RA and SpA outpatients referring to the Immuno-Rheumatology Institute at the S. Andrea hospital, Sapienza, University of Rome who had to undergo anti-TNFα therapy. RESULTS: Among the 169 enrolled subjects, 20 (12%) were potential occult HBV carriers (anti-HBc positive, HBsAg and HBV-DNA negative patients with or without anti-HBs). During the follow-up (mean ± SD 45 ± 22 months), aminotransferases and HBV-DNA, tested every two and six months respectively, did not change. CONCLUSION: This study confirms the substantial safety of anti-TNFα therapy in potential occult HBV carriers RA and SpA patients.


Assuntos
Antirreumáticos/farmacologia , Vírus da Hepatite B/fisiologia , Imunossupressores/farmacologia , Espondiloartropatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ativação Viral/efeitos dos fármacos , Idoso , Antirreumáticos/imunologia , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/imunologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Portador Sadio/sangue , Doença Crônica , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Espondiloartropatias/imunologia , Espondilite Anquilosante/tratamento farmacológico
12.
Case Rep Rheumatol ; 2013: 857694, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23984162

RESUMO

A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE). Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL) IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE) followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX) (375 mg/m(2) weekly for 4 weeks). Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

13.
Int J Immunopathol Pharmacol ; 25(1): 301-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22507346

RESUMO

The opportunity to induce remission/low disease activity in Rheumatoid Arthritis (RA) patients has been achieved in recent years by the adoption of more sensitive diagnostic methods [Magnetic Resonance Imaging (MRI), ultrasonography] and early aggressive treatments (combination of biologics and synthetic DMARDs). On the other hand, data are still scarce and contrasting about the management of long-term remission. The aim of this preliminary study is to evaluate whether the association of Methotrexate + Ciclosporine A (MTX + CSA) therapy in early RA (eRA) patients is able to maintain remission/low disease activity and avoid structural progression, evaluated by MRI. Etanercept was suspended in patients who reached remission/low disease activity and CSA+MTX therapy was introduced (T0), all patients continued to receive MTX; at this time MRI showed mild/moderate synovitis and erosions in all the patients; 1-year after (T1), a slight reduction in mean synovitis, bone edema and total score was observed, whereas the erosion score was unchanged. The mean DAS44 remained stable from T0 to T1 and 6/7 patients maintained a low disease activity score. No side effects were reported. These results confirm the good clinical efficacy and safety of the combination therapy CSA+MTX in eRA patients and demonstrate a parallel arrest of structural damage evaluated by MRI 1-year after etanercept suspension.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ciclosporina/administração & dosagem , Imunoglobulina G/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Metotrexato/administração & dosagem , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/patologia , Quimioterapia Combinada , Etanercepte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Biol Regul Homeost Agents ; 25(3): 397-403, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22023764

RESUMO

To retrospectively evaluate safety and efficacy of long-term treatment with Cyclosporine A (CSA) in patients with systemic lupus erythematosus (SLE) poorly responsive to treatment with corticosteroids (CCS) and/or conventional disease-modifying anti-rheumatic drugs (DMARDs), SLE patients who had received CSA-based induction and maintenance regimens according to disease activity were recorded. Efficacy was assessed using the SLE Disease Activity Index (SLEDAI) and laboratory analyses. Forty SLE patients (including 18 with lupus nephritis, 11 with neurological involvement and 7 with overlap syndromes (4 Sjögren's syndrome, 2 myasthenia gravis and 1 Behçet's disease) were recorded. According to baseline SLEDAI, 30 patients had severe and 10 moderate SLE. Mean SLEDAI scores and relevant laboratory values significantly reduced from baseline (22∓10 vs 5∓6; P < 0.002) during the follow-up period (8∓2 years; range 1-15). Twenty-three (57.5 percent) patients achieved excellent (improvement in the range 70-100 percent) response to treatment (10 of whom were subsequently maintained on CSA monotherapy), 14 (35 percent) had good-fair (improvement in the range 25-69 percent) response and 3 (7.5 percent) had to interrupt therapy (including CSA) for disease worsening. Mild and transient adverse events occurred in 15 (37 percent) patients, including hypertrichosis (17.5 percent), gum hypertrophy (17.5 percent) hypertension (12.5 percent), abdominal pain (7.5 percent), and dyslipidemia (5 percent), but treatment interruption was not required. Low-dose CSA together with other drugs is effective to induce, or as monotherapy to maintain, long-term (at least 2 years) remission, and is generally well tolerated in patients with moderate or severe SLE poorly responsive to CCS and/or conventional DMARDs. Furthermore, the favourable effect of CSA treatment may allow to spare more cytotoxic drugs.


Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo
15.
Int J Immunopathol Pharmacol ; 24(4): 983-91, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22230404

RESUMO

A young woman presenting respiratory infections, polyarthritis, severe neutropenia, and increased serum IgM was treated with intravenous immunoglobulin (IVIG) with good clinical and laboratory outcome followed by a loss of efficacy. The increased serum IgM associated to recurrent infections and autoimmune manifestations suggested the diagnosis of a hyper-IgM syndrome (HIGMs). The frequency of peripheral T cells, the expression of CD40 on the patients' B cells and CD40L on T cells and the activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase (UNG) at mRNA level was comparable to controls. In contrast, the frequency of B cells was one half of the healthy control and all cells showed an atypical phenotype. Although AID and UNG were normal, class-switch recombination was not very efficient because circulating switched memory were reduced and, once stimulated with CpG, generated less antibody-secreting cells than controls. An increase in serum B Lymphocytes stimulator (BLyS) was also found. The patient presented a peculiar clinical and immunological phenotype fitting for many aspects of both HIGM4 and Common Variable Immunodeficiency (CVID). These findings underline the need to better explore the complex link between these two diseases.


Assuntos
Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/diagnóstico , Imunoglobulina M/sangue , Neutropenia/imunologia , Infecções Respiratórias/imunologia , Adulto , Linfócitos B/imunologia , Biomarcadores/sangue , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/terapia , Ilhas de CpG/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/complicações , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunofenotipagem , Neutropenia/terapia , Fenótipo , Valor Preditivo dos Testes , Infecções Respiratórias/terapia , Linfócitos T/imunologia , Regulação para Cima
16.
G Ital Med Lav Ergon ; 32(2): 154-61, 2010.
Artigo em Italiano | MEDLINE | ID: mdl-20684436

RESUMO

There is no universally approved method in the scientific literature to identify subjects exposed to asbestos and divide them in classes according to intensity of exposure. The aim of our work is to study and develope an algorithm based on the findings of occupational anamnestical information provided by a large group of workers. The algorithm allows to discriminate, in a probabilistic way, the risk of exposure by the attribution of a code for each worker (ELSA Code--work estimated exposure to asbestos). The ELSA code has been obtained through a synthesis of information that the international scientific literature identifies as the most predictive for the onset of asbestos-related abnormalities. Four dimensions are analyzed and described: 1) present and/or past occupation; 2) type of materials and equipment used in performing working activity; 3) environment where these activities are carried out; 4) period of time when activities are performed. Although it is possible to have informations in a subjective manner, the decisional procedure is objective and is based on the systematic evaluation of asbestos exposure. From the combination of the four identified dimensions it is possible to have 108 ELSA codes divided in three typological profiles of estimated risk of exposure. The application of the algorithm offers some advantages compared to other methods used for identifying individuals exposed to asbestos: 1) it can be computed both in case of present and past exposure to asbestos; 2) the classification of workers exposed to asbestos using ELSA code is more detailed than the one we have obtained with Job Exposure Matrix (JEM) because the ELSA Code takes in account other indicators of risk besides those considered in the JEM. This algorithm was developed for a project sponsored by the Italian Armed Forces and is also adaptable to other work conditions for in which it could be necessary to assess risk for asbestos exposure.


Assuntos
Amianto/efeitos adversos , Asbestose/epidemiologia , Mesotelioma/epidemiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Pleurais/epidemiologia , Algoritmos , Asbestose/complicações , Asbestose/prevenção & controle , Humanos , Itália/epidemiologia , Mesotelioma/etiologia , Mesotelioma/prevenção & controle , Metanálise como Assunto , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/prevenção & controle , Valor Preditivo dos Testes , Medição de Risco , Inquéritos e Questionários
17.
Clin Immunol ; 134(2): 113-20, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19846344

RESUMO

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.


Assuntos
Anticorpos Antivirais/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Separação Celular , Etanercepte , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/sangue , Vacinas contra Influenza/uso terapêutico , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Clin Microbiol Infect ; 16(8): 1282-4, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19886902

RESUMO

Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.


Assuntos
Interferon gama/metabolismo , Interleucina-2/metabolismo , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose/diagnóstico , Adulto , Feminino , Humanos , Masculino
19.
Int J Immunopathol Pharmacol ; 22(2): 447-54, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19505397

RESUMO

The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40 percent) patients showed a total remission, DAS44 from 5 (T0) to 1.4 (T1); p<0.02, whereas the other 12/20 (60 percent) showed an improvement, without complete remission, DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40 percent of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Articulação da Mão/efeitos dos fármacos , Imunoglobulina G/administração & dosagem , Imageamento por Ressonância Magnética , Receptores do Fator de Necrose Tumoral/administração & dosagem , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Artrografia , Esquema de Medicação , Quimioterapia Combinada , Edema/tratamento farmacológico , Edema/patologia , Etanercepte , Feminino , Articulação da Mão/patologia , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão , Índice de Gravidade de Doença , Sinovite/tratamento farmacológico , Sinovite/patologia , Fatores de Tempo , Resultado do Tratamento
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