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1.
Eur Rev Med Pharmacol Sci ; 26(10): 3407, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35647819

RESUMO

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (7): 2631-2638-DOI: 10.26355/eurrev_202204_28501-PMID: 35442479, published online on 15 April 2022. After publication, at the request of the Italian Ministry of Health, the authors asked to insert the following statement in the Acknowledgments section: "This research was funded by the Italian Ministry of Health (RC 2022)". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/28501.

2.
Eur Rev Med Pharmacol Sci ; 26(7): 2631-2638, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35442479

RESUMO

OBJECTIVE: Temporary COVID-19 hotels have been established in Italy to assist the homeless people that test positive for SARS-CoV-2 and require isolation. This observational study aimed to investigate the characteristics of the subjects who were isolated at the Casa tra Noi COVID-19 hotel in Rome between October 2020 and May 2021 and to estimate the duration of SARS-CoV-2 positivity according to their main socio-demographic, behavioural and clinical features. SUBJECTS AND METHODS: Socio-demographic data, clinical history, and anamnestic data of guests were collected by the clinicians reviewing the medical documentation and face-to-face interviewing. Nasopharyngeal swabs were performed every 7 days and the presence of SARS-CoV-2 was assessed by RT-PCR. Median duration of SARS-CoV-2 positivity according to socio-demographic, behavioral factors and clinical condition was calculated. RESULTS: The 196 guests (161 males, 82.1%) had a median age of 41 years (IQR: 30-53), and were mostly African (87, 44.4%). Only asymptomatic/paucisymptomatic infections were observed. Almost half of the individuals (84, 42.9%) were affected by at least one co-morbidity, the frequency of which was higher among women (57.1% vs. 39.8%, p=0.06). The date of the negative SARS-CoV-2 molecular test was known for 144 guests (73.5%). Among these, the median duration of positivity was 21 days (IQR: 14-26) and did not significantly vary with age, country of origin, smoking status, alcohol or drug abuse. Among the co-morbidities, only infectious diseases significantly modified the duration of positivity, which increased from 21 to 34 days (p=0.013). CONCLUSIONS: Hotel guests were frequently affected by physical/mental co-morbidities. Duration of SARS-CoV-2 positivity was significantly prolonged only in individuals affected by an infectious disease.


Assuntos
COVID-19 , Adulto , Infecções Assintomáticas , COVID-19/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Cidade de Roma/epidemiologia , SARS-CoV-2
3.
Geochem Geophys Geosyst ; 20(8): 4059-4072, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31762710

RESUMO

Anhydrous phase B and stishovite formed directly from olivine in experiments at 14 GPa and 1400 °CThe structure of anhydrous phase B is determined ab initio from precession electron diffraction tomography in transmission electron microscopyElastic and seismic properties of anhydrous phase B are calculated.


We have performed an extensive characterization by transmission electron microscopy (including precession electron diffraction tomography and ab initio electron diffraction refinement as well as electron energy loss spectroscopy) of anhydrous phase B (Anh­B) formed directly from olivine at 14 GPa, 1400 °C. We show that Anh­B, which can be considered as a superstructure of olivine, exhibits strong topotactic relationships with it. This lowers the interfacial energy between the two phases and the energy barrier for nucleation of Anh­B, which can form as a metastable phase. We have calculated the elastic and seismic properties of Anh­B. From the elastic point of view, Anh­B appears to be more isotropic than olivine. Anh­B displays only a moderate seismic anisotropy quite similar to the one of wadsleyite.


Anhydrous phase B (Anh­B) is a dense magnesium silicate with composition (Mg, Fe)14Si5O24, which is expected to form in Mg­rich or Si­depleted regions of the mantle. We show that due to strong crystallographic similarities with the crystal structure of olivine, it can form directly from it as a metastable phase. We show that Anh­B exhibits a moderate seismic anisotropy, which makes its detection difficult in the mantle.

4.
Geochem Geophys Geosyst ; 19(3): 582-594, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29937698

RESUMO

Scanning precession electron diffraction is an emerging promising technique for mapping phases and crystal orientations with short acquisition times (10-20 ms/pixel) in a transmission electron microscope similarly to the Electron Backscattered Diffraction (EBSD) or Transmission Kikuchi Diffraction (TKD) techniques in a scanning electron microscope. In this study, we apply this technique to the characterization of deformation microstructures in an aggregate of bridgmanite and ferropericlase deformed at 27 GPa and 2,130 K. Such a sample is challenging for microstructural characterization for two reasons: (i) the bridgmanite is very unstable under electron irradiation, (ii) under high stress conditions, the dislocation density is so large that standard characterization by diffraction contrast are limited, or impossible. Here we show that detailed analysis of intracrystalline misorientations sheds some light on the deformation mechanisms of both phases. In bridgmanite, deformation is accommodated by localized, amorphous, shear deformation lamellae whereas ferropericlase undergoes large strains leading to grain elongation in response to intense dislocation activity with no evidence for recrystallization. Plastic strain in ferropericlase can be semiquantitatively assessed by following kernel average misorientation distributions.

5.
Eur J Surg Oncol ; 43(7): 1365-1371, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28274663

RESUMO

OBJECTIVES: No clear evidence of which surgical procedure should be performed for early stage mesothelioma is available to date. We analyzed our 10-year experience in the treatment of early stage mesothelioma with surgery and Hyperthermic IntraTHOracic Chemotherapy. METHODS: We retrospectively analyzed all cases of histologically proven epithelioid or biphasic IMIG stage I and II mesothelioma that we operated between 2005 and 2014. We performed an open pleurectomy and partial decortication of any visible lesion on the visceral pleura in all cases and both diaphragm and pericardium were always spared; Hyperthermic IntraTHOracic Chemotherapy was ran using Cisplatin 80 mg/m2 and Doxorubicin 25 mg/m2 at a target temperature of 42.5 °C for 60 min. RESULTS: We operated on 26 patients (23 male and 3 female); epithelioid tumor was diagnosed in 23 cases. Twelve patients were in IMIG stage I and 14 in IMIG stage II; median overall survival for all patients, stage I and II were 35.6, 46 and 23 months respectively and disease free survival was 18, 18 and 16 months respectively. Our results for stage I were better than those reported in literature and were similar for stage II. We observe no 30- and 90- mortality and the rate of severe complication (all CTCAE stage 3) were 30%; the median postoperative stay was 7.5 days. CONCLUSIONS: Our lung sparing approach for the treatment of pleural mesothelioma in early stages allows promising long term outcomes with a complete sparing of pulmonary and diaphragmatic function. Larger studies are needed to confirm our good results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Hipertermia Induzida , Tempo de Internação , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Neoplasias Pleurais/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Procedimentos Cirúrgicos Torácicos
6.
Cytopathology ; 25(6): 404-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24251636

RESUMO

OBJECTIVE: The majority of patients with lung cancer are treated on the basis of a diagnosis made from the analysis of a small tumour biopsy or a cytological sample and histotype is becoming a critical variable in clinical workup as it has led to the introduction of newer biologically targeted therapies. Consequently, simply classifying cancers as small cell lung cancers or non-small cell lung cancers is no longer sufficient. METHODS: From 2009 to 2011, a review of the histo-cytological database was conducted to identify all small biopsy and cytology specimens collected for diagnostic purposes in patients with a thoracic lesion. In total, 941 patients were studied by examining exfoliative and/or aspirative cytological samples. To establish the accuracy of these methods, cytological and biopsy diagnoses were compared with each other and with subsequent resection specimens when available. Moreover, during the diagnostic workup, we examined a validated panel of immunohistochemical markers. RESULTS: The diagnostic concordance of pre-operative diagnoses with surgical samples was high in both cytology and biopsy samples [κ = 0.71, confidence interval (CI) = 0.6-0.81; P < 0.0001 and κ = 0.61, CI = 0.41-0.82; P < 0.0001 respectively; good agreement] but concordance between cytology and biopsy was moderate (κ = 0.5, CI = 0.43-0.54; P < 0.0001). Immunohistochemistry-aided diagnoses were definitive for histotype in 92.8% of both cytology (206/222) and biopsy (155/167) specimens. CONCLUSION: We found that lung cancer diagnosis and subtyping of cytology and biopsy samples are highly feasible and concordant; thus, the diagnostic approach to lung cancer does not require more invasive procedures.


Assuntos
Citodiagnóstico/métodos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Idoso , Feminino , Técnicas Histológicas , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
7.
Br J Cancer ; 101(11): 1869-75, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19935800

RESUMO

BACKGROUND: Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value. METHODS: Tumour-infiltrating lymphocytes (CD4, CD8, Foxp3), mast cells (MCs) (tryptase and chymase), microvessel count (MVC) and VEGF were determined by immunohistochemistry in two series of MPM patients: 60 patients treated with intra-pleural preoperative IL-2 and 33 patients untreated. RESULTS: Tryptase MCs, and CD8 and Foxp3 lymphocytes were significantly increased in the IL-2-treated group, whereas MVC was significantly lower in the same group. Moreover, in the IL-2-treated group, greater tryptase+MCs and greater Foxp3 lymphocytes were associated with improved and poorer clinical outcomes, respectively. Notably, when these two immunological parameters were combined, they predicted outcomes more effectively. CONCLUSIONS: This study showed that IL-2 treatment leads to a significant increase of immunological parameters, concomitantly with a reduction in vasculature, providing new insight into the cancer mechanisms mediated by IL-2. Moreover, these results suggest that tryptase-positive MCs and Foxp3+ lymphocytes predict clinical outcomes in IL-2-treated patients, highlighting the critical role of the inflammatory response in mesothelioma cancer progression.


Assuntos
Interleucina-2/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Imuno-Histoquímica , Interleucina-2/imunologia , Linfócitos/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Mastócitos/imunologia , Mesotelioma/irrigação sanguínea , Mesotelioma/imunologia , Mesotelioma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/imunologia , Neoplasias Pleurais/irrigação sanguínea , Neoplasias Pleurais/imunologia , Neoplasias Pleurais/patologia , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Triptases/imunologia
9.
Pathologica ; 100(1): 25-30, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18686523

RESUMO

Glomus tumours are uncommon neoplasms usually arising in the dermis and subcutaneous tissues where glomus bodies are generally found. Occasionally glomus tumours can occur in extracutaneous sites such as the gastrointestinal tract, bone, genitourinary system and respiratory tract. Primary pulmonary glomus tumours are very rare (only 17 cases reported in the literature), and are often confused with other solid neoplasms such as carcinoids, hemangiopericytomas and tumours belonging to the family of Ewing's sarcoma/primitive neuroectodermal tumours. We present a case of a primary pulmonary glomus tumour originating in the right main bronchus with focal invasion of the submucosa in a 69-year-old man. Histological and immunohistochemical features are reported. The current literature is briefly reviewed, with special attention to differential diagnosis and malignancy criteria.


Assuntos
Tumor Glômico/patologia , Neoplasias Pulmonares/patologia , Idoso , Humanos , Masculino
10.
Ann Ig ; 20(2): 171-8, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-18590048

RESUMO

Discharge against medical advice (DAMA) may put patients at risk of adverse health outcomes and often generate hospital readmission. A retrospective case-control study (2000-2004) of all DAMA in Veneto Region hospitals was carried out to determine the baseline characteristics of patients who leaves hospital. During the 5-years study period, the overall DAMA rates were 0.8 from ordinary hospitalization and 0.2 from daily. Prediction of patients at risk of DAMA may be possible with several defined variables and this analysis represent an instrument that should facilitate the development of successful strategies to reduce DAMA for high-risk patients.


Assuntos
Alta do Paciente/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Programática de Saúde , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade
12.
J Antimicrob Chemother ; 61(4): 884-91, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18252692

RESUMO

OBJECTIVES: Antibacterial efficacy of azithromycin could be improved by achieving higher concentrations at the sites of infection. Azithromycin extended release (azithromycin-ER) formulation was developed to enable a higher dosage of 2 g to be administered as a single oral dose without decreasing the safety profile. The aim of this study was to compare the pharmacokinetics of azithromycin in serum, epithelial lining fluid (ELF), alveolar macrophages (AMs) and lung tissue following a single oral dose of azithromycin-ER or azithromycin immediate release (azithromycin-IR) formulation. PATIENTS AND METHODS: A total of 64 patients, diagnosed with lung cancer, requiring open-chest surgery for lung resection, completed the study. Subjects were randomized to receive oral administration of either a single 2 g dose of azithromycin-ER (32 subjects) or a single 500 mg dose of azithromycin-IR (32 subjects). Simultaneously, subjects within each treatment group were randomized to one of eight specific nominal post-dose time points for bronchoalveolar lavage and lung tissue sampling. Results For azithromycin-IR formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue was 3.1, 2.3, 1674 mg.h/L and 130 mg.h/kg, respectively. For azithromycin-ER formulation, the AUC(0-24) in serum, ELF, AMs and lung tissue were 10.0, 17.6, 7028 mg.h/L and 505 mg.h/kg, respectively. The AUC(0-24) ratio following administration of azithromycin-ER relative to azithromycin-IR was 3.2, 7.7, 4.2 and 3.9 in serum, ELF, AMs and lung tissue, respectively. CONCLUSIONS: Within the first 24 h, a single 2 g azithromycin-ER dose produced dose-related increase in systemic exposure compared with a single 500 mg azithromycin-IR dose, which resulted in higher levels of azithromycin in ELF, AMs and lung tissue. Both formulations had similar safety profiles. By achieving high azithromycin exposure early in the course of treatment, without compromising tolerability, azithromycin-ER shows the potential for improved antibacterial efficacy compared with azithromycin-IR.


Assuntos
Administração Oral , Antibacterianos/farmacocinética , Azitromicina/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Líquido da Lavagem Broncoalveolar/química , Preparações de Ação Retardada/farmacocinética , Feminino , Humanos , Pulmão/química , Macrófagos Alveolares/química , Masculino , Pessoa de Meia-Idade , Soro/química , Distribuição Tecidual
13.
J Cardiovasc Surg (Torino) ; 48(3): 369-74, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17505443

RESUMO

AIM: T4 non-small cell lung cancer (NSCLC) is commonly considered a contraindication to surgery, indeed chemo-radiotherapy achieves a poor survival rate. We have reviewed our experience with T4 NSCLC patients who underwent surgery with the aim of debating the indications and results of surgical treatment in this highly selected group of patients. METHODS: We investigated a cohort of 60 patients, 49 men and 11 women, who underwent surgery for NSCLC from January 1998 to December 2002 and whose pathological staging was T4N0-2M0. The median age was 65 years (range 46-82). The tumors were classified T4 for the following reasons: intralobar satellite metastasis in 24 cases, direct mediastinum invasion in 18 cases, malignant pleural effusion in 7 cases, involvement of the superior vena cava in 4 cases, marginal invasion of the vertebral body in 3 cases, involvement of the carena in 3 cases and invasion of the left atrium in 1 case. Thirteen patients had undergone neo-adjuvant chemotherapy while 39 underwent adjuvant therapies. RESULTS: Thirty-two patients resulted with N0 disease, 5 with N1 and 23 with N2 disease. Forty patients relapsed (27 systemic and 13 local relapses). The mean survival was 20 months. Of the examined parameters only metastatic nodal involvement was significantly associated with a worse prognosis (P=0.007). CONCLUSION: Surgery for T4 NSCLC may be effective in those patients without mediastinal (N2) lymph node involvement. The prognosis was neither affected by the subtype of T4 tumor nor by the use of adjuvant therapies and/or neoadjuvant chemotherapy but only by the N status. In the preoperative work-up, every possible effort should be made to achieve a careful evaluation of lymph-nodal status (primarily by mediastinoscopy and video operative staging).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Seleção de Pacientes , Pneumonectomia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfonodos/patologia , Metástase Linfática/diagnóstico , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias/métodos , Radioterapia Adjuvante , Medição de Risco , Fatores de Risco , Cirurgia Torácica Vídeoassistida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Thorax ; 61(9): 828-9, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16936239

RESUMO

Recurrence in the contralateral lung of patients who have undergone pneumonectomy for lung cancer is often not surgically treatable. Percutaneous radiofrequency ablation (RFA) of tumours is an emerging minimally invasive technique which has recently been used in the treatment of lung cancer. The case history is presented of a patient who had previously undergone pneumonectomy in whom recurrence of lung cancer was treated by RFA. The procedure was performed under CT guidance and was uneventful. At follow up 9 months later the tumour appeared to have ablated. To our knowledge, no similar case has previously been reported in the literature.


Assuntos
Ablação por Cateter/métodos , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Pneumonectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
16.
J Cardiovasc Surg (Torino) ; 47(1): 89-93, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16434954

RESUMO

AIM: Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors. METHODS: The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out. RESULTS: The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages. CONCLUSIONS: The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.


Assuntos
Timoma/patologia , Neoplasias do Timo/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Timoma/classificação , Timoma/metabolismo , Timoma/mortalidade , Neoplasias do Timo/classificação , Neoplasias do Timo/metabolismo , Neoplasias do Timo/mortalidade
17.
Surg Endosc ; 19(12): 1644-7, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16206002

RESUMO

BACKGROUND: Preoperative procedures are often necessary to localize pulmonary nodules during thoracoscopic resection in order to reduce the necessity of resorting to thoracotomy. The aim of this report is to describe the strategy we developed to limit preoperative techniques without reducing the thoracoscopic success rate of localization. METHODS: Between January 2000 and December 2003, 183 patients underwent video thoracoscopic resection of small pulmonary nodules. The patients were divided into two groups on the basis of the radiological features of the nodule. The subjects in group 1 were operated on directly, and endothoracic ultrasonography was performed when necessary. The subjects in group 2 underwent preoperative radionuclide labeling of the nodule. RESULTS: In group 1, 112 out of 119 nodules (94%) were localized. Twenty-five out of 32 lesions, neither visible nor palpable, were found by endothoracic ultrasonography. In group 2, we localized 62 out of 64 nodules (97%). CONCLUSIONS: Currently, we cannot completely avoid preoperative labeling techniques for thoracoscopic resection of small pulmonary nodules. However, correct patient selection may limit this necessity, without an increased conversion rate to thoracotomy, if endothoracic ultrasonography is available.


Assuntos
Neoplasias Pulmonares/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Toracoscopia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/patologia
18.
Br J Dermatol ; 153(3): 531-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16120138

RESUMO

BACKGROUND: Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-alpha antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. OBJECTIVES: To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti-TNF-alpha therapy. METHODS: Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0.4 and 42.8 were treated with infliximab for 30-42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg(-1) intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-alpha, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. RESULTS: Eighteen of 20 psoriatic patients achieved > 50% improvement and 14 of 20 patients attained > 75% improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50% improvement (ACR-50) and 16 of 20 patients attained > 75% improvement (ACR-75) at 10 weeks. TNF-alpha did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P < 0.01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-alpha in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. CONCLUSIONS: Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-alpha serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Citocinas/sangue , Fatores Imunológicos/uso terapêutico , Adulto , Análise de Variância , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/imunologia , Esquema de Medicação , Selectina E/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Infliximab , Interleucina-6/sangue , Articulações/diagnóstico por imagem , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/sangue
19.
Br J Cancer ; 93(4): 453-7, 2005 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-16091764

RESUMO

Osteopontin (OPN) is a multifunctional protein, which has recently been shown to be linked to tumorigenesis, progression and metastasis in different malignancies. Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few predictors of outcome, the purpose of this study was to evaluate if OPN might be involved in NSCLC's biology and therefore represent a prognostic marker and a target for new therapeutic trials. Immunohistochemistry was used to detect OPN expression, evaluated as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumours with low (<20%) from tumours with high (> or =20%) OPN expression. A statistically significant correlation between high levels of OPN and shorter overall (P = 0.034) and disease-free (P = 0.011) survival in our patients was shown. Our results support the hypothesis that high OPN expression is a significantly unfavourable prognostic factor for the survival of patients with stage I NSCLC. This conclusion has notable importance in terms of the biological characterization of early-stage tumours and therapeutic opportunities.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Neoplasias Pulmonares/química , Sialoglicoproteínas/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteopontina , Prognóstico , Sialoglicoproteínas/biossíntese
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