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1.
Clin Infect Dis ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38059510

RESUMO

The early administration of appropriate antibiotic therapy is crucial for the survival of patients with bacteremia. Current research focuses on improving analytical times through technology while there have been very few efforts to improve post-analytical times even though they represent 40% of the time between blood taking and appropriate treatment administration. One of the clues is the efficiency and appropriateness of the result communication system. Here, we review all delays in the whole process with the aim of improving time to appropriate treatment administration. We discuss causes for long times to adjust treatment once microbiological results are released. We argue that that the pervasive health information system in this organization serves as both a bottleneck and a rigid framework to focus on. Finally, we explore how should be conceived the next generation hospital information systems to effectively assist the doctors in treating patients with bacteremia.

2.
J Biol Regul Homeost Agents ; 32(2): 397-405, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29685025

RESUMO

The aim of this study was to compare the quality of the coronal seal, using an in vitro bacterial invasion test, of three different root canal filling systems. Twenty-seven freshly extracted mandibular premolars were selected and divided into three experimental groups (G1, G2 and G3 n=7) and two control groups (Ct+ and Ct- n=3). All teeth in the experimental groups were prepared using NiTi Mtwo rotating instruments and then the endodontic treatments were completed using the three-tested warm guttapercha root filling techniques: Microseal (G1), Thermafil (G2) and System B (G3). All root filling techniques were performed using the same endodontic sealer (Pulp Canal Sealer). Three teeth were instrumented and not filled, serving as positive controls (Ct+) and the last three teeth, with intact crowns and no endodontic treatment, served as negative controls (Ct-). All samples were mounted in a two-chamber apparatus and exposed to Enterococcus faecalis performing a bacterial infiltration test. All samples were observed for a maximum period of 60 days checking for turbidity of the BHI broth on a daily basis recording when contamination occurred. A quantitative evaluation of the bacterial CFU/ml was performed using the URO-QUICK™ system. On day 32 an overall value was recorded of contamination of 42.85% for group G1, 71.42% for G2 and 42.85% for G3; after 60 days, the final contamination result was 85.71% for group G1, and 100% for both G2 and G3 groups. Considering the number of contaminated samples at the end of the observation period, the three techniques showed no statistically significant differences. The study highlighted the bacterial permeability of gutta-percha/seal barrier, underlining the importance of an effective coronal restoration to ensure a durable seal after root canal treatment.


Assuntos
Cavidade Pulpar/microbiologia , Materiais Restauradores do Canal Radicular , Obturação do Canal Radicular/métodos , Bactérias , Humanos , Permeabilidade
3.
Clin Exp Immunol ; 190(2): 226-234, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28708268

RESUMO

Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1-12 months for adult patients and every 3-6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients.


Assuntos
Síndromes de Imunodeficiência/fisiopatologia , Pneumopatias/complicações , Sistema Respiratório/fisiopatologia , Adulto , Agamaglobulinemia/fisiopatologia , Assistência Ambulatorial , Infecções Assintomáticas/epidemiologia , Criança , Imunodeficiência de Variável Comum/fisiopatologia , Europa (Continente) , Feminino , Humanos , Imunização Passiva , Imunoglobulina G/uso terapêutico , Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Pneumopatias/diagnóstico , Pneumopatias/imunologia , Pneumopatias/prevenção & controle , Masculino , Prontuários Médicos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Espirometria
4.
Clin Mol Allergy ; 13(1): 16, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26240517

RESUMO

BACKGROUND: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. METHODS: In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. RESULTS: Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. CONCLUSIONS: These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

5.
Diabetologia ; 56(8): 1856-66, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23616239

RESUMO

AIM/HYPOTHESIS: Monocytes/macrophages play important roles in adipose and vascular tissues and can be polarised as inflammatory M1 or anti-inflammatory M2. We sought to analyse monocyte polarisation status in type 2 diabetes, which is characterised by chronic inflammation. METHODS: We enrolled 60 individuals without diabetes and 53 patients with type 2 diabetes. We quantified standard monocyte subsets defined by cluster of differentiation (CD)14 and CD16. In addition, based on the phenotype of polarised macrophages in vitro, we characterised and quantified more definite M1 (CD68(+)CCR2(+)) and M2 (CX3CR1(+)CD206(+)/CD163(+)) monocytes. We also analysed bone marrow (BM) samples and the effects of granulocyte-colony stimulating factor (G-CSF) stimulation in diabetic and control individuals. RESULTS: We found no alterations in standard monocyte subsets (classical, intermediate and non-classical) when comparing groups. For validation of M1 and M2 phenotypes, we observed that M2 were enriched in non-classical monocytes and had lower TNF-α content, higher LDL scavenging and lower transendothelial migratory capacity than M1. Diabetic patients displayed an imbalanced M1/M2 ratio compared with the control group, attributable to a reduction in M2. The M1/M2 ratio was directly correlated with waist circumference and HbA1c and, among diabetic patients, M2 reduction and M1/M2 increase were associated with microangiopathy. A decrease in M2 was also found in the BM from diabetic patients, with a relative M2 excess compared with the bloodstream. BM stimulation with G-CSF mobilised M2 macrophages in diabetic but not in healthy individuals. CONCLUSIONS/INTERPRETATION: We show that type 2 diabetes markedly reduces anti-inflammatory M2 monocytes through a dysregulation in bone-marrow function. This defect may have a negative impact on microangiopathy.


Assuntos
Medula Óssea/imunologia , Diabetes Mellitus Tipo 2/imunologia , Angiopatias Diabéticas/imunologia , Monócitos/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia
6.
Mol Ecol ; 22(20): 5148-61, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23962255

RESUMO

Determining the timing, extent and underlying causes of interspecific gene exchange during or following speciation is central to understanding species' evolution. Antarctic notothenioid fish, thanks to the acquisition of antifreeze glycoproteins during Oligocene transition to polar conditions, experienced a spectacular radiation to >100 species during Late Miocene cooling events. The impact of recent glacial cycles on this group is poorly known, but alternating warming and cooling periods may have affected species' distributions, promoted ecological divergence into recurrently opening niches and/or possibly brought allopatric species into contact. Using microsatellite markers and statistical methods including Approximate Bayesian Computation, we investigated genetic differentiation, hybridization and the possible influence of the last glaciation/deglaciation events in three icefish species of the genus Chionodraco. Our results provide strong evidence of contemporary and past introgression by showing that: (i) a substantial fraction of contemporary individuals in each species has mixed ancestry, (ii) evolutionary scenarios excluding hybridization or including it only in ancient times have small or zero posterior probabilities, (iii) the data support a scenario of interspecific gene flow associated with the two most recent interglacial periods. Glacial cycles might therefore have had a profound impact on the genetic composition of Antarctic fauna, as newly available shelf areas during the warmer intervals might have favoured secondary contacts and hybridization between diversified groups. If our findings are confirmed in other notothenioids, they offer new perspectives for understanding evolutionary dynamics of Antarctic fish and suggest a need for new predictions on the effects of global warming in this group.


Assuntos
Evolução Biológica , Mudança Climática , Hibridização Genética , Perciformes/genética , Adaptação Fisiológica/genética , Animais , Regiões Antárticas , Teorema de Bayes , Fluxo Gênico , Variação Genética , Genética Populacional , Genótipo , Repetições de Microssatélites , Modelos Genéticos , Perciformes/classificação
7.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(1): 70-2, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24003538

RESUMO

Here, we report a case of a 38-year-old woman with a history of systemic sarcoidosis who developed cutaneous verrucous sarcoidosis simulating a squamous cell carcinoma. This modality of presentation is unusual in both caucasic patients and in woman and may represent a diagnostic challenge for dermatologists.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Sarcoidose/epidemiologia , Dermatopatias/epidemiologia , Neoplasias Cutâneas/diagnóstico , Adulto , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Paraceratose/epidemiologia , Paraceratose/patologia , Sarcoidose/patologia , Dermatopatias/patologia
8.
Open Forum Infect Dis ; 10(12): ofad627, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156051

RESUMO

Background: The objective of this study was to expand real-life data on cefiderocol efficacy to treat multidrug-resistant Acinetobacter baumannii infections. Methods: This was a retrospective monocentric study including patients hospitalized (>24 hours) at Policlinico Tor Vergata, Rome, Italy, between May 1, 2021, and September 1, 2022, treated with cefiderocol (>48 hours). The primary objective was early clinical improvement at 48-72 hours from cefiderocol start; secondary objectives were clinical success (composite outcome of infection resolution and 14-day survival), breakthrough infection, overall 30-day mortality, and cefiderocol-related adverse events. Results: Eleven patients were enrolled; 91% males (10/11), with a median age (interquartile range [IQR]) of 69 (59-71) years, 91% had ≥1 comorbidity, and 72.7% (8/11) were hospitalized in internal medicine wards. Six patients with bloodstream infection (54.5%; 4 primary, 2 central line-associated), 2 with pneumonia (18.2%), 2 with urinary tract infections (18.2%), and 1 with intra-abdominal infection (9.1%) were treated. Four patients (36.3%) presented with septic shock at cefiderocol start. Cefiderocol was used as monotherapy in 3/11 patients (27.3%), was combined with colistin in all the other 8 cases, and was used in triple combination with tigecycline in 2 patients. The median duration of treatment (IQR) was 12 (10-14) days. Early clinical improvement was documented in 8/11 patients (72.7%), clinical success in 8/11 patients (72.7%). Overall 30-day mortality was 27.3% (3/11), with death occurring a median (IQR) of 19 (17.5-20.5) days after the start of therapy. No cefiderocol-related adverse events were documented. Conclusions: Cefiderocol seems to be a safe and effective option for multidrug-resistant Acinetobacter baumannii infections.

9.
Diabetologia ; 54(4): 945-53, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21165593

RESUMO

AIMS/HYPOTHESIS: Bone marrow (BM)-derived endothelial progenitor cells (EPC) promote tissue healing and angiogenesis, whereas altered EPC biology may favour diabetic complications. We tested the hypothesis that diabetes impairs the contribution of BM-derived cells at sites of wound healing. METHODS: Four weeks after induction of diabetes in C57BL/6 mice, hindlimb skin wounds were created and monitored by digital imaging and histology. Circulating EPCs were quantified by flow cytometry before and after wounding. In separate experiments, bone marrow from C57BL/6 mice constitutively producing green fluorescent protein (GFP) was transplanted into myeloablated wild-type mice before induction of diabetes. We quantified proliferation, apoptosis and endothelial differentiation of tissue GFP(+) cells. Net recruitment of GFP(+) cells was estimated by correcting the number of tissue GFP(+) cells at each time point for basal levels, apoptosis and proliferation rates. RESULTS: Diabetes delayed wound healing, with reduced granulation tissue thickness and vascularity, and increased apoptosis. Circulating EPC levels were not modified by 4 week diabetes and/or skin wounding. BM-derived EPCs (GFP(+)vWf(+) [von Willebrand factor] cells) within the granulation tissue were significantly reduced in diabetic compared with control mice. BM-derived GFP(+) cells showed increased apoptosis and decreased proliferation in diabetic versus non-diabetic wound tissues. Estimated net recruitment of BM-derived GFP(+) cells was reduced on day 1 after wounding in diabetic mice. CONCLUSIONS/INTERPRETATION: Diabetic-delayed wound healing was associated with defective recruitment, survival and proliferation of BM-derived progenitor cells. Local treatments aimed at restoring EPC homing and survival might improve tissue healing in diabetes.


Assuntos
Células da Medula Óssea/citologia , Diabetes Mellitus/terapia , Células-Tronco/citologia , Células-Tronco/fisiologia , Cicatrização/fisiologia , Animais , Proliferação de Células , Sobrevivência Celular/fisiologia , Camundongos , Transplante de Células-Tronco
10.
Diabetes Obes Metab ; 13(8): 718-25, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21410861

RESUMO

AIMS: In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D). METHODS: This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded. RESULTS: Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms. CONCLUSION: Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Idoso , Estudos Cross-Over , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/induzido quimicamente , Angiopatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Células Endoteliais/fisiologia , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Detemir , Insulina Glargina , Insulina de Ação Prolongada , Masculino , Resultado do Tratamento
11.
Eur Respir J ; 35(2): 418-25, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20123847

RESUMO

Pulmonary hypertension is a progressive and disabling disease with as yet unclear pathogenesis, limited treatment options and poor prognosis. This is why the discovery of new pathogenic mechanisms and therapeutic strategies are needed. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial homeostasis, as well as physiological and pathological angiogenesis. Experimental and clinical studies have been conducted to understand the possible contribution of EPCs to the pathogenesis of pulmonary hypertension. Conflicting results have been obtained regarding the protective versus harmful effects of EPCs on the pulmonary vasculature. However, preliminary clinical trials using EPC-based therapies in patients with pulmonary hypertension show benefit of this approach, thus revealing EPCs as potential therapeutic targets. This review critically summarises the complex and conflicting data on EPCs and pulmonary hypertension, in both humans and animals, putting them into the context of lung (patho)physiology. The resulting scenario identifies EPCs as a novel and fascinating tool to study pathophysiology and therapy in the setting of pulmonary hypertension.


Assuntos
Células Endoteliais/citologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/terapia , Células-Tronco/citologia , Animais , Ensaios Clínicos como Assunto , Hemodinâmica , Homeostase , Humanos , Hipóxia , Camundongos , Modelos Biológicos , Neovascularização Patológica , Fenótipo , Prognóstico , Estrutura Terciária de Proteína
12.
Br J Cancer ; 100(4): 601-7, 2009 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-19190632

RESUMO

Advanced ovarian carcinoma in early progression (<6 months) (AOCEP) is considered resistant to most cytotoxic drugs. Gemcitabine (GE) and oxaliplatin (OXA) have shown single-agent activity in relapsed ovarian cancer. Their combination was tested in patients with AOCEP in phase II study. Fifty patients pre-treated with platinum-taxane received q3w administration of OXA (100 mg m(-2), d1) and GE (1000 mg m(-2), d1, d8, 100-min infusion). Patient characteristics were a : median age 64 years (range 46-79),and 1 (84%) or 2 (16%) earlier lines of treatment. Haematological toxicity included grade 3-4 neutropaenia (33%), anaemia (8%), and thrombocytopaenia (19%). Febrile neutropaenia occurred in 3%. Non-haematological toxicity included grade 2-3 nausea or vomiting (34%), grade 3 fatigue (25%),and grade 2 alopecia (24%). Eighteen (37%) patients experienced response. Median progression-free (PF) and overall survivals (OS) were 4.6 and 11.4 months, respectively. The OXA-GE combination has high activity and acceptable toxicity in AOCEP patients. A comparison of the doublet OXA-GE with single-agent treatment is warranted.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Platina/administração & dosagem , Taxoides/administração & dosagem , Gencitabina
13.
Ann Oncol ; 20(6): 1105-12, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19174452

RESUMO

BACKGROUND: Epoetin (EPO) administration reduces the need for transfusion. Identifying patients at high risk of anemia requiring red blood cell (RBC) transfusion is needed. This multicentric phase III trial tested epoetin alpha (EPOalpha) administration according to our risk model on the basis of three clinical parameters: hemoglobin (Hb) <12 g/dl, lymphocytes 1. PATIENTS AND METHODS: Patients >or=18 years with chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0, lymphocyte count, and PS. The primary end point was transfusion rate; secondary end points included overall survival (OS), safety, and quality of life. RESULTS: From September 2000 to January 2005, 218 patients (median age 64 years, 42.7% males) with principally breast cancer, sarcoma, or lung carcinoma were included. In total, 93% patients had PS >1 and 35% had

Assuntos
Anemia/tratamento farmacológico , Eritropoetina/administração & dosagem , Hematínicos/administração & dosagem , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Quimioprevenção , Epoetina alfa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Proteínas Recombinantes , Fatores de Risco
14.
Clin Exp Rheumatol ; 27(5): 814-21, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19917165

RESUMO

OBJECTIVES: We tested whether Behçet's disease (BD) is characterized by alterations of circulating endothelial progenitor cells (EPCs),which are involved in vascular homeostasis and repair. METHODS: We enrolled 30 BD patients and 27 matched healthy controls. EPCs were defined and measured by flow cytometry according to the expression of CD34, CD133 and KDR. RESULTS: We show that BD patients had significantly lower levels of CD34+KDR+ and CD34+CD133+KDR+ EPCs than controls. We found significant negative correlations between EPC phenotypes and BD duration, while there were positive correlations between CD34+KDR+ EPCs and both BD activity scores and C-reactive protein. The lower EPC levels with increasing disease duration was shown in univariate analysis and in multivariable analysis adjusted for possible confounders. CONCLUSION: This is the first report that BD is associated with progressive EPC decline. Reduction of EPCs may represent a mechanism of induction and/or progression of vascular injury in these patients.


Assuntos
Síndrome de Behçet/sangue , Células Endoteliais/metabolismo , Células-Tronco/metabolismo , Antígeno AC133 , Adulto , Antígenos CD , Antígenos CD34 , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Estudos de Casos e Controles , Citometria de Fluxo , Glicoproteínas , Humanos , Masculino , Peptídeos , Índice de Gravidade de Doença , Receptor 2 de Fatores de Crescimento do Endotélio Vascular
15.
J Biol Regul Homeost Agents ; 23(4): 239-50, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20003763

RESUMO

B-chronic lymphocytic leukemia (B-CLL) is a malignant disorder characterized by the accumulation of the leukemic cells in the G0-G1 phase of the cell cycle and expressing high levels of the anti-apoptotic protein Bcl-2. Since we observed that the treatment of autoimmune complications with Cyclosporine A (CsA) determined in some CLL patients an improvement not only of the autoimmune phenomena, but also of the leukemic process, we evaluated the in vitro cytotoxicity of CsA as compared to Dexamethasone (Dex) on leukemic cells. Leukemic cells obtained from 32 B-CLL patients showed a heterogeneous pattern of spontaneous apoptosis at 24 h interval and this pattern permitted to identify: Group 1 (14/32) with high (>20%) apoptotic rate and Group 2 (18/32) with low cell death. CsA and Dex increased cell death in both groups with a different timing by an apoptotic mechanism that does not involve Bcl-2. Furthermore, in Group 2, CsA-induced apoptosis was significant higher than that observed with Dex both at 4 and 24 h. We suggest that, in B-CLL, CsA has a significant pro-apoptotic activity manifested also in patients with low spontaneous apoptosis. Our observations might be taken into account to consider new therapeutic strategies in B-CLL.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Ciclosporina/farmacologia , Dexametasona/farmacologia , Imunossupressores/farmacologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fase G1/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fatores de Tempo , Células Tumorais Cultivadas
16.
J Endocrinol Invest ; 32(11): 889-94, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19502771

RESUMO

We previously confirmed that high altitude (HA) exposure can modify the number and function of immune cells, leading to a disruption in the homeostatic regulation of T helper1 (Th1)/T helper2 (Th2) immune responses. Our aim was to evaluate possible relationships between the stress response and immunological parameters during HA exposure. Thirteen healthy women spent 21 days at 5050 m. Before (SL1), the first and the 21st day at HA (HA1 and HA2, respectively), and the day after returning at sea level (SL2), we collected blood samples for immunologic parameters, and 24-h urine samples for norepinephrine, epinephrine, and cortisol. Norepinephrine and cortisol significantly increased (p<0.01) at HA1 and HA2 compared to SL1, while epinephrine did not change. At HA1, CD3+ T-cell fell significantly (p<0.001) with respect to SL1, owing to a significant (p<0.001) CD4+ T-cell reduction, while CD16+ and CD56+ increased (p<0.001) at HA2 compared to SL1. The expression of interferon-gamma (IFN-gamma) decreased (p<0.0005) at HA1 and HA2 with respect to SL1. At HA1 different lymphocyte subset (CD3+, CD4+, CD19+) were well correlated with epinephrine (p<0.05), whereas in analyzing the combined data (SL1-HA1-HA2-SL2), CD3+ (r=-0.310), CD4+ (r=-0.332), CD16+ (r=0.404), and CD56+ (r=0.373) demonstrated moderate but significant correlations (p<0.05) with norepinephrine. Moreover, norepinephrine levels were inversely correlated (r=-0.591; p<0.001) with IFN-gamma expression, a typical Th1 cytokine. We suggest that the sympatho-adrenal axis may have a role on the immunologic adaptations observed during HA exposure, and specifically on the observed impairment of the Th1/Th2 immune balance.


Assuntos
Doença da Altitude/imunologia , Altitude , Epinefrina/metabolismo , Hidrocortisona/metabolismo , Norepinefrina/metabolismo , Células Th1/imunologia , Células Th2/imunologia , Complexo CD3/sangue , Antígeno CD56/imunologia , Feminino , Proteínas Ligadas por GPI , Humanos , Subpopulações de Linfócitos/imunologia , Receptores de IgG/imunologia , Adulto Jovem
17.
Thorax ; 63(9): 795-802, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18344408

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease, including neoplastic transformation. Few tissue markers for epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present, no information is available on its expression in IPF. METHODS: SCCA and transforming growth factor beta (TGFbeta) expression in surgical lung biopsies from 22 patients with IPF and 20 control cases was examined. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGFbeta expression. SCCA and TGFbeta epithelial expression was evaluated by immunohistochemistry and reverse transcription-PCR (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGFbeta expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT-PCR. RESULTS: SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In patients with IPF, SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p = 0.02), expression of TGFbeta (r = 0.78, p<0.0001) and with carbon monoxide transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGFbeta expression, with a peak at 24 h. CONCLUSION: Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.


Assuntos
Antígenos de Neoplasias/metabolismo , Pulmão/patologia , Fibrose Pulmonar/patologia , Serpinas/metabolismo , Adulto , Antígenos de Neoplasias/genética , Biópsia , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serpinas/genética , Fator de Crescimento Transformador beta/metabolismo
18.
Diabetes Metab ; 34(1): 33-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18069031

RESUMO

AIM: To evaluate a standardized protocol for maintaining near-normoglycaemia during labour and delivery in women with type 1 diabetes. METHODS: Over a nine-year period (1997-2005), 229 pregnancies in 174 women with type 1 diabetes were delivered at one centre. The same regimen was used for the induction of labour (group 1) and in women admitted in spontaneous labour (group 2): 10% dextrose (80ml/h) intravenous was given along with short-acting insulin, starting at 1IU/h intravenous via an infusion pump. Capillary blood glucose (CBG) was determined hourly, and the insulin infusion rate was modified accordingly. RESULTS: Labour was induced in 85 cases (37%) and spontaneous in 23 cases (10%), and an elective C-section was performed in 121 cases (53%). Maternal glycaemia during labour was 6.1+/-1.6 (range: 3.9-9.2)mmol/l in group 1, and 6.9+/-2.0 (range: 4.7-12.0)mmol/l in group 2. Maternal glycaemia at delivery was 5.8+/-1.5 (range: 3.4-9.4) and 6.3+/-1.9 (range: 4.1-11.4)mmol/l in groups 1 and 2, respectively. Women who underwent an elective C-section were not included in the standardized protocol and had higher glycaemia at delivery 7.1+/-2.0 (range: 2.7-13.5)mmol/l. Neonatal hypoglycaemia occurred in 30 infants (13%), and was only associated with preterm delivery. CONCLUSION: Using a standardized simple protocol during labour, maternal glycaemia was maintained within a near-normal range in 80-85% of cases.


Assuntos
Glicemia/metabolismo , Parto Obstétrico , Diabetes Mellitus Tipo 1/fisiopatologia , Trabalho de Parto/fisiologia , Gravidez em Diabéticas/sangue , Adulto , Densidade Óssea , Feminino , Hemoglobinas Glicadas/análise , Humanos , Recém-Nascido , Gravidez
19.
Leukemia ; 21(5): 1060-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17361229

RESUMO

Using polymerase chain reaction (PCR)-based sequence-specific primers, the killer immunoglobulin-like receptor (KIR) genotypes of 35 patients with natural killer (NK)-type lymphoproliferative disease of granular lymphocytes and of 50 normal subjects were investigated to evaluate whether genes coding for activating KIRs were more frequently detected in patients with NK-lymphoproliferative disease of granular lymphocytes (LDGL). Genotype frequency indicated that the most frequently found gene content was eight genes in controls and 14 in patients (P<0.05). The KIR genotype analysis revealed that patient and, surprisingly, control KIR genotypes preferentially consisted of type B haplotypes characterized by the presence of multiple-activating KIRs. Evidence was also provided that the same KIR genotype was shared by a variable number of patients. Interestingly, the recurrent genotypes observed in the patient group were not found in controls. Concerning inhibitory genes, KIR2DL5a and 2DL5b were more frequently detected in patients than in controls (P<0.01), likely representing a discrete feature of the genetic repertoire of the patients. KIR gene repertoire analysis in patients suggests that the susceptibility to NK-LDGL might be related to the presence of activating KIR genes and supports the concept that these receptors may be involved in the priming of granular lymphocytes (GL) proliferation. Population analysis might disclose a genetic background predisposing to this disease.


Assuntos
Células Matadoras Naturais/patologia , Transtornos Linfoproliferativos/imunologia , Receptores Imunológicos/genética , Adulto , Idoso , Feminino , Frequência do Gene , Genes MHC Classe I , Genótipo , Humanos , Células Matadoras Naturais/imunologia , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Receptores KIR , Receptores KIR2DL5
20.
J Radiol ; 89(3 Pt 1): 325-30, 2008 Mar.
Artigo em Francês | MEDLINE | ID: mdl-18408631

RESUMO

PURPOSE: To assess the value of standard double reading of whole body CT in the management of polytrauma patients. MATERIALS AND METHODS: Prospective study between January and July 2005. Two senior radiologists with expertise in trauma imaging, blinded to clinical findings, reviewed 105 initial CT examinations of polytrauma patients. These examinations had initially been interpreted by the on-call radiologist. The second interpretations were performed within 12 hours of admission, and were considered the gold standard. RESULTS: A total of 105 patients were included with 82 males (78%) and 23 females (22%), aged between 2 and 83 years. The level of admission was graded III (n=64), II (n=30) and I (n=11). The second reading identified 3 lesions that were not initially described, each requiring a change in management, including splenic rupture (n=1), thoracic spine fracture (n=1) and epidural hematoma (n=1), with no unfavorable impact on mortality. Additional errors in the initial interpretation were identified: peripheral fractures (n=38), chest (n=36), brain (n=31), abdominal (n=28), spine (n=19) and maxillofacial (17) lesions and contrast extravasation (n=6). CONCLUSION: Based on the large number and severity of some lesions missed at initial interpretation of whole body CT of polytrauma patients, we recommend standard double reading of these examinations.


Assuntos
Traumatismo Múltiplo/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos
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