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Vascular anomalies can cause both emotional and physical distress to patients, particularly children. The paediatric laser service at Great Ormond Street Hospital (GOSH) treats a range of dermatological conditions including a variety of vascular anomalies, excess hair growth and disfiguring scars. The laser team at GOSH has 25 years of experience in treating a wide variety of paediatric dermatological conditions using various laser therapies. With over 600 new referrals for laser therapy and over 1000 laser procedures each year the GOSH laser team has vast amounts of experience with both common and rare conditions. Excellent clinical outcomes continue to be delivered, and new treatment therapies are constantly being developed to treat more recalcitrant lesions. The adverse effect rates experienced by the GOSH laser patients have been decreasing over the past two decades, reaching the low rate of 0.8% per treated patients per year. This remarkable achievement has been continuously improved by integrating specific and standardized laser protocols for each patient treated, to ensure efficacious and safe laser treatment delivery. Treating vascular anomalies with laser therapy creates significant positive results among the paediatric population, thus laser therapy at GOSH makes a significant impact upon children's lives with both rare and common vascular anomalies.
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Terapia a Laser , Anormalidades da Pele/terapia , Malformações Vasculares/terapia , Criança , Pré-Escolar , Feminino , Hemangioma/terapia , Humanos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Masculino , Síndromes Neurocutâneas/terapiaRESUMO
BACKGROUND: B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. RESULTS: A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). CONCLUSION: The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Cetuximab/administração & dosagem , Cisplatino/administração & dosagem , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
Mounting evidence of the occurrence of direct and indirect interactions between the human blood fluke, Schistosoma mansoni, and the gut microbiota of rodent models raises questions on the potential role(s) of the latter in the pathophysiology of hepatointestinal schistosomiasis. However, substantial differences in both the composition and function between the gut microbiota of laboratory rodents and that of humans hinders an in-depth understanding of the significance of such interactions for human schistosomiasis. Taking advantage of the availability of a human microbiota-associated mouse model (HMA), we have previously highlighted differences in infection-associated changes in gut microbiota composition between HMA and wildtype (WT) mice. To further explore the dynamics of schistosome-microbiota relationships in HMA mice, in this study we (i) characterize qualitative and quantitative changes in gut microbiota composition of a distinct line of HMA mice (D2 HMA) infected with S. mansoni prior to and following the onset of parasite egg production; (ii) profile local and systemic immune responses against the parasite in HMA as well as WT mice and (iii) assess levels of faecal inflammatory markers and occult blood as indirect measures of gut tissue damage. We show that patent S. mansoni infection is associated with reduced bacterial alpha diversity in the gut of D2 HMA mice, alongside expansion of hydrogen sulphide-producing bacteria. Similar systemic humoral responses against S. mansoni in WT and D2 HMA mice, as well as levels of faecal lipocalin and markers of alternatively activated macrophages, suggest that these are independent of baseline gut microbiota composition. Qualitative comparative analyses between faecal microbial profiles of S. mansoni-infected WT and distinct lines of HMA mice reveal that, while infection-induced alterations of the gut microbiota composition are highly dependent on the baseline flora, bile acid composition and metabolism may represent key elements of schistosome-microbiota interactions through the gut-liver axis.
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Neutrophils are the first immune cells recruited for defence against invading pathogens; however, their dysregulated activation and subsequent release of the enzyme human neutrophil elastase is associated with several, inflammation-based, diseases. Herein, we describe a FRET-based, tri-branched (one quencher, three fluorophores) near infrared probe that provides an intense OFF/ON amplified fluorescence signal for specific detection of human neutrophil elastase. The probe allowed selective detection of activated neutrophils and labelling of neutrophil extracellular traps.
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Armadilhas Extracelulares , Neutrófilos , Humanos , Elastase de LeucócitoRESUMO
There is a strong correlation between SARS-CoV-2 and the onset of autoimmune neurological disease with atypical clinical presentation, characterized by limited response to medical therapy, likely caused by the underlying mechanism of the virus itself. In situations like these, after the failure of pharmacological therapy, therapeutic apheresis, including immunoadsorption, can be pursued. Treatments with IMMUSORBA TR-350 columns have proven to be particularly effective in managing refractory forms of post-Covid-19 nephropathies, leading to complete recovery of disability and elimination of neurological signs and symptoms. We discuss the case of a patient with chronic inflammatory polyradiculopathy post-Covid-19, resistant to medical therapy, effectively treated with immunoadsorption.
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Remoção de Componentes Sanguíneos , COVID-19 , Nefropatias , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , COVID-19/complicações , COVID-19/terapia , SARS-CoV-2RESUMO
OBJECTIVES: The aim of this study is to examine if urban pollution can modify indices of genotoxic damage. METHODS: Research of articles inherent in the evaluation of these alterations. Differents categories of exposed workers are included in the study (cases, in number of 7287) and compaired with no exposed workers (controls, in number of 8054). To calculate the result of meta-analysis the Effect Size (ES) was used and the confidence interval was calculated. RESULTS: In this category we evaluated 54 studies and we observed significantly differences in the complex. CONCLUSIONS: Starting from the individual variables analysis investigated, between exposed and not exposed group, we underline the utility to deepen the studies concerning of these parameters, to appreciate their benefits and to safeguard health of exposed workers.
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Poluentes Atmosféricos/efeitos adversos , Dano ao DNA , Exposição Ocupacional/efeitos adversos , Saúde da População Urbana , HumanosRESUMO
Aim of the study is to evaluate whether occupational exposure to low doses of pollutants present in the air of the city selected for the study could cause alterations in peripheral blood counts in workers of the Municipal Police with outdoor tasks vs workers with indoor tasks. 279 non smoker males were enrolled and divided on the basis of their different kind of task. The dosage of air pollutants was carried out through the use of personal air samplers on a representative group of workers. Data obtained were subject to statistical evaluation consisting of Homogeneity of variance test, ANOVA univariate test with post hoc Bonferroni correction, Jonckheere-Terpstra test and multiple linear regression analysis. The differences were considered statistically significant when p values were lower than 0.05. Mean levels of RBC, HB, MCHC, WBC and neutrophil cells were significantly higher in traffic policemen and police drivers compared to controls (workers with indoor tasks). Mean levels of MCV, MCH and lymphocytes were significantly lower in traffic policemen and police drivers compared to controls. These results were confirmed by Multiple linear regression test and Jonckheere-Terpstra test. The results suggest that prolonged occupational exposure to low doses of traffic pollutants can alter some lines of the hematopoietic system in exposed workers.
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Poluentes Atmosféricos , Veículos Automotores , Exposição Ocupacional , Polícia , Adulto , Poluentes Atmosféricos/análise , Contagem de Células Sanguíneas , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análiseRESUMO
BACKGROUND: Purpose of this study is to evaluate and to compare the excretion of urinary 1-hydroxypyrene (1-OHPu) in traffic policemen (TP) and drivers (D) of a large Italian city and to evaluate the existence and the degree of correlation between airborne exposure to 15 different polycyclic aromatic hydrocarbons (PAHs) and 1-OHPu levels in the examined population. METHODS: 192 male workers, 115 TP and 77 D, were monitored for 1-HOPu. A subgroup of non-smoking workers (subgroup B: 59 TP and 15 D) was also examined and 15 environmental PAHs was monitored through the personal samplings for the measurement of the particulate phase. RESULTS: The 1-OHPu levels and the values of personal airborne exposure to PAHs were significantly higher among non-smoking TP than among non-smoking D (p < 0.05). In subgroup B the levels of environmental exposure to all the 15 PAHs measured in TP and only 6 of 15 PAHs measured in D were significantly correlated with the values of 1-OHPu (p < 0.05). CONCLUSIONS: Our results suggest that the use of 1-OHPu as an indicator of exposure to PAHs is reliable also for what concerns the study of the low-dose work-related exposure in urban outdoor workers.
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Poluentes Atmosféricos/urina , Monitoramento Ambiental , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Pirenos/urina , Adulto , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polícia , Meios de Transporte , Saúde da População UrbanaRESUMO
INTRODUCTION: To evaluate the radiological sequelae of coronavirus disease (COVID-19) in a mid-term follow-up and investigate their relationship with clinical-radiological findings. METHODS: This prospective study included COVID-19 patients who underwent a CXR three months after discharge. The relationship between CXR score at three months after discharge and clinical findings and previous CXR scores, at admission and before the discharge, were evaluated. Then, based on mid-term follow-up CXR score, patients were divided in Group A (score = 0) and Group B (score≥1), and clinical-radiological findings were compared between two Groups. Finally, we calculated the CXR scores at admission and before the discharge with the highest sensitivity and specificity to predict normal and abnormal CXR score at mid-term follow-up. RESULTS: The study included 119 patients, mean age 65.9 ± 14.6 years. The oxygen saturation (SaO2) (p = 0.0006), the days of hospitalization (p < 0.0001) and the CXR score before the discharge (p = 0.0091) were independent factors to predict the mid-term follow-up CXR score. The Group A, 59 (49.6%) patients, had CXR scores at admission and before the discharge lower than Group B. The CXR scores at admission and before the discharge with the highest sensitivity and specificity to predict normal and abnormal CXR score at mid-term follow-up were, respectively, 3 and 2 (p < 0.0001). CONCLUSIONS: The radiological abnormalities were present in about half patients three months after discharge, which had higher age, previous CXR scores and longer hospitalization. The SO2, days of hospitalization and previous CXR scores were independent factors for predicting the CXR at three months. IMPLICATIONS FOR PRACTICE: The radiologist with CXR could play a central role in mid to long-term follow-up of COVID-19, assessing the radiological sequelae of patients and identifying those who might require a closer follow-up.
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COVID-19 , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia Torácica , Estudos Retrospectivos , Raios XRESUMO
This work introduces an experimental activity related to the realization of an epossidic nanostructured material that develops the function of covering for electronic circuits in aeronautical field. This covering meets the demand of protection of these circuits from possible troubles of electromagnetic nature. In order to realize this covering we used an epoxy resin as matrix (Epon 828) loaded with conductive nanofillers or carbon nanotubes (Cnts). To check the efficiency of the coating we have considered the carbon black, filler widely used as a conductive covering for screenings. We have considered different percentages of the different fillers, precisely 0.1%, 0.25% and 0.5% wt (% valued in comparison to the weight of the resin). From every mixture 12 samples have been obtained (the size of every sample is 10 mm x 10 mm x 10 mm). Every sample has been subjected to electrical measurements, that have concerned the measurement of current intensity and resistance (so as to allow the evaluation of the enhancement of the conductivity), through the application of different values of voltage. The results have demonstrated that the epoxy matrix loaded with Cnts yields higher values of electrical conductivity than the same matrix loaded with carbon black.
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Oral mucositis (OM) is a very frequent and potentially severe complication experienced by patients receiving chemotherapy and/or radiotherapy, which often leads to significant morbidity and mortality, and decreased quality of life, and is very costly. Despite its severity and prevalence, there is no standard recognised management today. The aim of this open clinical trial is to evaluate the efficacy and compliance of a new spray compound containing sodium hyaluronate (SH) and a pool of collagen precursor amino acids (AAs) combined with sodium hyaluronate (SH) to manage radio/chemotherapy-induced OM. Twenty-seven consecutive patients with OM were treated according to the manufacturers instructions. At time T0 (baseline before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0100) and (ii) severity of OM scored according to WHO Mucositis scale. The treatment efficacy was evaluated on i) pain score, ii) clinical resolution index (CRI) and iii) patient compliance at times T01 (after 2 hours), T1 (after 24 hours), T2 (after 72 hours), T3 (after 7 days) and T4 (after 14 days). Results showed that painful symptoms were significantly reduced after only 2 hours of spray administration compared with baseline measurements (p less than 0.0001; z=-4.541). A progressive reduction of pain through the 2 weeks was also noted (p less than 0.0001). Patient lesions treated with SH-Asbased spray also significantly improved after 72 hours of treatment (p=0.0051; z=-2.803). During the two-week observation, all patients significantly improved from the baseline (p less than 0.0001) and progressively ameliorated their ability to swallow foods and liquids. The compliance of all patients to the product was very good, and at the end of the study there were no adverse effects. The results suggest that the SHAAs-based spray accelerates lesion healing and above all helps to manage mucositis pain, especially in terms of immediate pain relief (after 2 hours from application). Although further randomized controlled studies are recommended, our findings suggest that frequent applications of this spray may offer rapid and effective pain management, aiding faster mucosal wound healing.
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Aminoácidos/administração & dosagem , Antineoplásicos/efeitos adversos , Colágeno/biossíntese , Ácido Hialurônico/administração & dosagem , Radioterapia/efeitos adversos , Estomatite/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicina/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Leucina/administração & dosagem , Lisina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prolina/administração & dosagem , Estomatite/etiologiaRESUMO
OBJECTIVE: In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. METHODS: The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. RESULTS: In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). CONCLUSION: The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.
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Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Rim/fisiopatologia , Idoso , Albuminúria/fisiopatologia , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Humanos , Imunoglobulina G/urina , Testes de Função Renal , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: To investigate the impact on bone and muscle of pathological conditions involving only one of the upper limbs, it is important to know the physiological differences due to the dominance effect. AIM: To evaluate any physiological differences between dominant and non-dominant upper limbs in terms of bone mineral density (BMD), muscle mass, and muscle density at different levels. SUBJECTS AND METHODS: The study considered 60 right-handed healthy adults, 30 men and 30 women. Cortical BMD, muscle area, and muscle density were investigated by pQCT-XCT-3000 Stratec at the proximal radius, trabecular and total BMD at the distal radius, and trabecular and cortical BMD at the second phalanx of the third finger. Hand grip strength was also measured. RESULTS: No significant differences in BMD were found between the dominant and non-dominant upper limbs at any of the sites considered, in men or women. Muscle density was also similar on the two sides, whereas muscle area at the proximal radius was significantly lower on the non-dominant side in both men [4177.5+/-475.1 vs 4009.3+/-552.7 mm2; Delta%: 4.1%; 95% confidence interval (CI) 1.7%-6.5%] and women (2903.9+/-470.9 vs 2720.3+/-411.7 mm2; Delta%: 6.1%; 95%CI 4.3%-7.9%). Hand grip strength proved greater on the right side in both men (48.5+/-8.8 vs 45.2+/-8.7 kg; Delta% 7.1; p<0.001) and women (29.1+/-4.3 vs 27.0+/-5.1 kg; Delta% 7.1; p<0.001). CONCLUSION: The dominance effect does not seem to influence trabecular or cortical BMD at any of the sites in the upper limb. Muscle density is not modified by dominance, while muscle area is reduced on the non-dominant side and this should be borne in mind when the effect of pathological conditions on the body composition of a single forearm is investigated.
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Composição Corporal/fisiologia , Densidade Óssea , Dominância Cerebral/fisiologia , Rádio (Anatomia)/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologiaRESUMO
Metastatic melanoma is still associated with a poor prognosis, and there is increasing interest in immunotherapy alone or in combination with other adjuvant therapies. Γδ T lymphocytes play a pivot role in the immune response against cancer, but while γδ-based immunotherapy is already a clinical reality for several solid tumors, data on melanoma are still limited and fragmented. This systematic review presents preclinical and clinical evidence for a role of γδ T lymphocytes in immunotherapeutic strategies for advanced melanoma and discusses research state of the art and future perspectives. Current strategies focus on in vivo stimulation, and ex vivo adoptive therapy and vaccination; results are promising, but further studies are needed to better investigate the interactions in tumoral microenvironment and to improve clinical efficacy of immunotherapeutic protocols.
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BACKGROUND: Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)-resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy. METHODS: The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data. RESULTS: From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval [CI], 7.7-12.6) and 23.8 months (95% CI, 19.7-25.0) respectively. CONCLUSION: Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
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Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Tolerância a Radiação , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Diferenciação Celular , Ensaios de Uso Compassivo , Progressão da Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. METHODS: A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15 wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had significantly increased cortisol on d-1 ( approximately 5.2-folds) [median: 18.95 (95% CI: 11.20-39.4) microg/dl vs. 3.66 (1.94-6.82) microg/dl, p < 0.0001)] and d-7( approximately 1.7-folds) [12.0 (4.39-22.97) microg/dl vs. 7.8 (3.63-12.8) microg/dl, p = 0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 ( approximately 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p = 0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR = 14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile (OR = 4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant at univariate analysis). CONCLUSIONS: Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.
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Sistema Hipotálamo-Hipofisário/fisiologia , Recém-Nascido de muito Baixo Peso/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Timo/fisiopatologia , Hormônio Adrenocorticotrópico/sangue , Estudos Transversais , Feminino , Humanos , Hidrocortisona/sangue , Recém-Nascido , Masculino , Razão de Chances , Timo/anatomia & histologiaRESUMO
BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.
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Neoplasias Colorretais/genética , Metilação de DNA , Genes p16 , Genes p53 , Genes ras , Idoso , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Prognóstico , Regiões Promotoras Genéticas , Estudos ProspectivosRESUMO
BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.
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Neoplasias Colorretais/genética , Metilação de DNA , Genes p16 , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/genética , Neoplasias Colorretais/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estadiamento de Neoplasias , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression.