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1.
Phys Rev Lett ; 120(7): 072001, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29542981

RESUMO

The leading-order electromagnetic and strong isospin-breaking corrections to the ratio of K_{µ2} and π_{µ2} decay rates are evaluated for the first time on the lattice, following a method recently proposed. The lattice results are obtained using the gauge ensembles produced by the European Twisted Mass Collaboration with N_{f}=2+1+1 dynamical quarks. Systematic effects are evaluated and the impact of the quenched QED approximation is estimated. Our result for the correction to the tree-level K_{µ2}/π_{µ2} decay ratio is -1.22(16)%, to be compared to the estimate of -1.12(21)% based on chiral perturbation theory and adopted by the Particle Data Group.

2.
Eur J Gynaecol Oncol ; 38(3): 476-478, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29693897

RESUMO

Myeloid sarcoma (MS) is a rare tumor mass derived from the extramedullary proliferation of blasts of one or more of myeloid lineages. It usually occurs at an anatomical site other than the bone marrow (BM). Among the anatomical site which may be involved, female genital tract is a rare localization. When MS follows a previous history of myeloid pathology it is usually associated to a poor prognosis. To date this disease was managed with exploratory laparotomy or with surgical debulking. The authors report a case of laparosc6pic diagnosis of a pelvic myeloid sarcoma in a patient previously affected by acute mycloid leukemia, evidencing the importance of minimally invasive diagnosis and subsequent multidisciplinary management.


Assuntos
Neoplasias Pélvicas/patologia , Sarcoma Mieloide/patologia , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Pessoa de Meia-Idade
3.
J Neurophysiol ; 116(6): 2752-2764, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27683882

RESUMO

The vestibulosympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether changes in heart rate (HR) are associated with changes in BP are still not clear. We used manually activated pulses and oscillatory linear accelerations of 0.2-2.5 g along the naso-occipital, interaural, and dorsoventral axes in isoflurane-anesthetized, male Long-Evans rats. BP and HR were recorded with an intra-aortic sensor and acceleration with a three-dimensional accelerometer. Linear regressions of BP changes in accelerations along the upward, downward, and forward axes had slopes of ≈3-6 mmHg · g-1 (P < 0.05). Lateral and backward accelerations did not produce consistent changes in BP. Thus upward, downward, and forward translations were the directions that significantly altered BP. HR was unaffected by these translations. The VSR sensitivity to oscillatory forward-backward translations was ≈6-10 mmHg · g-1 at frequencies of ≈0.1 Hz (0.2 g), decreasing to zero at frequencies above 2 Hz (1.8 g). Upward, 70° tilts of an alert rat increased BP by 9 mmHg · g-1 without changes in HR, indicating that anesthesia had not reduced the VSR sensitivity. The similarity in BP induced in alert and anesthetized rats indicates that the VSR is relatively insensitive to levels of alertness and that the VSR is likely to cause changes in BP through modification of peripheral vascular resistance. Thus the VSR, which is directed toward the cardiovascular system, is in contrast to the responses in the alert state that can produce sweating, alterations in BP and HR, and motion sickness.


Assuntos
Aceleração , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Sistema Nervoso Simpático/fisiologia , Vestíbulo do Labirinto/fisiologia , Análise de Variância , Animais , Fenômenos Biomecânicos , Masculino , Orientação , Ratos , Ratos Long-Evans , Reflexo , Respiração
4.
Ann Oncol ; 26(1): 185-192, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361995

RESUMO

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Esplenomegalia/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Baço/patologia , Adulto Jovem
5.
Ann Oncol ; 25(1): 176-81, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24287938

RESUMO

BACKGROUND: Pathological fractures (PFs) occur in 10%-20% of patients with diffuse large B-cell lymphoma (DLBCL) of the bone. The clinical features and the effects of this severe complication on management and prognosis have not been previously analyzed in a large series. PATIENTS AND METHODS: The effects of PF on management and prognosis were reviewed in an international retrospective series of 373 patients with newly diagnosed bone DLBCL, comparing 78 patients with PF at presentation (group 'PF-BL') and 295 patients without PF ('controls'). RESULTS: At a median follow-up of 53 months (range 3-246), PF-BL patients exhibited lower rates of overall response (ORR, 78% versus 85%; P = 0.17), 5-year progression-free survival (PFS, 53 ± 6% versus 61 ± 3%; P = 0.02) and 5-year overall survival (OS, 54 ± 6% versus 68 ± 3%, P = 0.008) than controls. Initial surgical stabilization of the PF did not change therapeutic outcome (5-year OS: 45 ± 9% versus 54 ± 10%; P = 0.20). PF-BL patients referred to irradiation of the fractured bone before chemotherapy exhibited a significantly poorer outcome than patients managed with the inverse sequence (ORR: 52% versus 92%, P = 0.0005; 5-year OS: 22 ± 14% versus 64 ± 9%, P = 0.007). Multivariate analysis confirmed the independent association between PF and worse survival and the negative effect of radiotherapy as initial therapy. CONCLUSION: Fracture is an independent, adverse prognostic event in patients with bone DLBCL. Anthracycline-based chemotherapy followed by radiotherapy seems to be the better treatment sequence. Initial fracture stabilization does not seem to improve outcome; it should be used to improve patient's quality of life only if chemotherapy delays can be avoided.


Assuntos
Neoplasias Ósseas/patologia , Fraturas Ósseas/etiologia , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
6.
Genet Mol Res ; 13(3): 5138-42, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25061738

RESUMO

The Atlantic rainforest species Ocotea catharinensis, Ocotea odorifera, and Ocotea porosa have been extensively harvested in the past for timber and oil extraction and are currently listed as threatened due to overexploitation. To investigate the genetic diversity and population structure of these species, we developed 8 polymorphic microsatellite markers for O. odorifera from an enriched microsatellite library by using 2 dinucleotide repeats. The microsatellite markers were tested for cross-amplification in O. catharinensis and O. porosa. The average number of alleles per locus was 10.2, considering all loci over 2 populations of O. odorifera. Observed and expected heterozygosities for O. odorifera ranged from 0.39 to 0.93 and 0.41 to 0.92 across populations, respectively. Cross-amplification of all loci was successfully observed in O. catharinensis and O. porosa except 1 locus that was found to lack polymorphism in O. porosa. Combined probabilities of identity in the studied Ocotea species were very low ranging from 1.0 x 10-24 to 7.7 x 10-24. The probability of exclusion over all loci estimated for O. odorifera indicated a 99.9% chance of correctly excluding a random nonparent individual. The microsatellite markers described in this study have high information content and will be useful for further investigations on genetic diversity within these species and for subsequent conservation purposes.


Assuntos
Espécies em Perigo de Extinção , Loci Gênicos , Repetições de Microssatélites , Ocotea/genética , Alelos , Conservação dos Recursos Naturais , Marcadores Genéticos , Variação Genética , Genética Populacional , Heterozigoto , Ocotea/classificação , Floresta Úmida , Especificidade da Espécie
7.
Minerva Stomatol ; 63(4): 111-26, 2014 Apr.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-24705041

RESUMO

AIM: Aim of the review was to provide a literature overview of the birth defects of cleft lip and/or cleft palate (CL/P). METHODS: Through the use of the PubMed database items were collected that would provide information about the condition, leading to the discussion of the following topics: epidemiology, anatomical features, genetics, environmental factors, diagnosis and treatment. RESULTS: According to these data, the CL/P are the most common congenital malformations of the craniofacial region. There are different phenotypes and clinical features of this malformation, which differ according to the anatomical structures involved: cleft lip, cleft lip and cleft palate. The etiology is multifactorial and includes both genetic factors and environmental factors. For proper diagnosis and treatment it is important to complete a multidisciplinary approach to guide the patient from birth to the end of growth. Among the outstanding figures for the care of the anomaly are: the gynecologist, the pediatrician, the maxillofacial surgeon and orthodontist. Individuals with a cleft lip and/or cleft palate may experience problems in feeding, pronunciation, hearing and social integration, which can be corrected to a different extent by surgery, dental treatment, speech therapy and psychosocial interventions. CONCLUSION: Today the optimal treatment is difficult to find, because of the large variability of malformations and the subjective response of each patient to therapy.


Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Criança , Pré-Escolar , Fenda Labial/diagnóstico , Fenda Labial/etiologia , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico , Fissura Palatina/etiologia , Fissura Palatina/cirurgia , Humanos , Lactente , Recém-Nascido
8.
Pharmacogenomics J ; 13(4): 335-41, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22584460

RESUMO

Genetic heterogeneity in drug-metabolizing enzyme/transporter (DMET) genes affects specific drug-related cancer phenotypes. To investigate the relationships between genetic variation and response to treatment in acute myeloid leukemia (AML), we genotyped 1931 variants on DMET genes in 94 CD33-positive AML patients enrolled in a phase III multicenter clinical trial combining Gemtuzumab-Ozogamicin (GO) with Fludarabine-Cytarabine-Idarubicin (FLAI) regimen, with the DMET Plus platform. Two ADH1A variants showed statistically significant differences (odds ratio (OR)=5.68, P=0.0006; OR=5.35, P=0.0009) in allele frequencies between patients in complete/partial remission and patients without response, two substitutions on CYP2E1 (OR=0.13, P=0.001; OR=0.09, P=0.003) and one on SLCO1B1 (OR=4.68, P=0.002) were found to differently influence liver toxicity, and two nucleotide changes on SULTB1 and SLC22A12 genes correlated with response to GO (OR=0.24, P=0.0009; OR=2.75, P=0.0029). Genetic variants were thus found for the first time to be potentially associated with differential response and toxicity in AML patients treated with a combination of GO-FLAI regimen.


Assuntos
Enzimas/genética , Inativação Metabólica/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Citarabina/administração & dosagem , Enzimas/metabolismo , Feminino , Gemtuzumab , Heterogeneidade Genética , Genótipo , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
9.
Hematol Oncol ; 31(1): 34-40, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22473680

RESUMO

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Terapia de Salvação , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Cisplatino/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/cirurgia , Humanos , Ifosfamida/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transplante de Células-Tronco de Sangue Periférico , Prognóstico , Compostos Radiofarmacêuticos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Adulto Jovem , Gencitabina
10.
Minerva Stomatol ; 62(11-12): 431-46, 2013.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-24270203

RESUMO

The aim of this paper was to provide a literature review about the problems that can occur during orthodontic treatment. Using the PubMed database we collected items that would provide information regarding the direct consequences of the placement of an orthodontic appliance: coming to the discussion of the following topics: candida infections, the effects on the soft tissues, the effects on periodontal tissues and effects on hard tissues. The presence of appliances in the oral cavity increases the prevalence of people with candida, specifically the species Candida Albicans is the most frequently isolated. The balance between the clearance of the microorganism, the colonization and the state of candidiasis depends both on the virulence of the fungus, and the competence of the host immune system. On soft tissues, cases of ulceration of the upper jaw by a rapid palatal expander and pyogenic granuloma due to quad helix appliance have been reported. The second one is mostly observed on vestibular gingiva. The first one was found, however, in patients suffering from diabetes mellitus type 1 because of the tissue modifications induced by this pathological condition. The more severe periodontic effects are those caused by incorrect use of orthodontic elastic separators. Finally, the White Spot Lesions are the direct consequences of a wrong conditioning of enamel when attaching the bracket. They represent a first stage of caries in the positioning area of the bracket. The orthodontist is required to intercept these issues not to affect the success of the treatment.


Assuntos
Corrosão Dentária/efeitos adversos , Úlceras Orais/etiologia , Aparelhos Ortodônticos/efeitos adversos , Candida/classificação , Candida/isolamento & purificação , Candidíase Bucal/etiologia , Candidíase Bucal/microbiologia , Criança , Pré-Escolar , Cárie Dentária/etiologia , Esmalte Dentário/efeitos dos fármacos , Placa Dentária/etiologia , Diabetes Mellitus Tipo 1/complicações , Suscetibilidade a Doenças , Granuloma Piogênico/etiologia , Humanos , Lactente , Higiene Bucal , Periodontite/etiologia , Ácidos Fosfóricos/efeitos adversos , Lesões dos Tecidos Moles/etiologia , Especificidade da Espécie
11.
Opt Lett ; 37(23): 4832-4, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23202061

RESUMO

We report the experimental demonstration of a modulation instability (MI) process assisted by a periodic dispersion modulation in an optical fiber. We observe the spontaneous growth of more than 10 pairs of MI sidebands spanning over more than 10 THz thanks to a quasi-phase-matched process.

12.
Acta Biol Hung ; 63 Suppl 1: 5-18, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22453739

RESUMO

We have previously demonstrated that imidazole-4-acetic acid-ribotide (IAA-RP) is present in the mammalian brain and is an endogenous ligand at imidazoline binding sites. In the present study, we used a polyclonal antiserum to visualize IAA-RP-containing neurons in the rat caudoputamen. We observe IAA-RP-immunostained neurons scattered throughout the dorsal and ventral striatum. Most of these cells co-localize GABA, but none are parvalbumin-immunoreactive. In contrast, approximately 50% of the calbindin D28k-immunopositive striatal neurons co-localize IAA-RP. Electrophysiological studies using corticostriatal slices demonstrated that bath application of IAA-RP reversibly depresses the synaptically mediated component of field potentials recorded in the striatum by stimulation of cortical axons. Addition of competitive glutamate receptor antagonists completely blocks the response, confirming its association with glutamatergic transmission. Using paired-pulse stimuli, IAA-RP was shown to exert, at least in part, a presynaptic effect, but blockade of GABAA receptor-mediated transmission did not alter the response. Lastly, we show that this effect is attributable to imidazoline-1 receptors, and not to α2 adrenergic receptors. Since IAA-RP is an endogenous central regulator of blood pressure, and cardiovascular dysfunction is a common symptom associated with Parkinson's disease (PD), we speculate that IAA-RP-related abnormalities may underlie some of the autonomic dysfunction that occurs in PD.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Gânglios da Base/metabolismo , Imidazóis/metabolismo , Atividade Motora , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Ribosemonofosfatos/metabolismo , Animais , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/fisiopatologia , Calbindina 1 , Calbindinas , Estimulação Elétrica , Potenciais Evocados , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Receptores de Imidazolinas/metabolismo , Ligantes , Masculino , Microscopia de Fluorescência , Inibição Neural , Neurônios/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Transmissão Sináptica , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismo
13.
Blood Cancer J ; 12(1): 15, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35082295

RESUMO

Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37-8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18-10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.


Assuntos
Mieloma Múltiplo/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Idoso , Deleção Cromossômica , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Prognóstico
14.
J Neurophysiol ; 105(3): 1266-75, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21228308

RESUMO

Imidazole-4-acetic acid-ribotide (IAA-RP), an endogenous agonist at imidazoline receptors (I-Rs), is a putative neurotransmitter/regulator in mammalian brain. We studied the effects of IAA-RP on excitatory transmission by performing extracellular and whole cell recordings at Schaffer collateral-CA1 synapses in rat hippocampal slices. Bath-applied IAA-RP induced a concentration-dependent depression of synaptic transmission that, after washout, returned to baseline within 20 min. Maximal decrease occurred with 10 µM IAA-RP, which reduced the slope of field extracellular postsynaptic potentials (fEPSPs) to 51.2 ± 5.7% of baseline at 20 min of exposure. Imidazole-4-acetic acid-riboside (IAA-R; 10 µM), the endogenous dephosphorylated metabolite of IAA-RP, also produced inhibition of fEPSPs. This effect was smaller than that produced by IAA-RP (to 65.9 ± 3.8% of baseline) and occurred after a further 5- to 8-min delay. The frequency, but not the amplitude, of miniature excitatory postsynaptic currents was decreased, and paired-pulse facilitation (PPF) was increased after application of IAA-RP, suggesting a principally presynaptic site of action. Since IAA-RP also has low affinity for α(2)-adrenergic receptors (α(2)-ARs), we tested synaptic depression induced by IAA-RP in the presence of α(2)-ARs, I(1)-R, or I(3)-R antagonists. The α(2)-AR antagonist rauwolscine (100 nM), which blocked the actions of the α(2)-AR agonist clonidine, did not affect either the IAA-RP-induced synaptic depression or the increase in PPF. In contrast, efaroxan (50 µM), a mixed I(1)-R and α(2)-AR antagonist, abolished the synaptic depression induced by IAA-RP and abolished the related increase in PPF. KU-14R, an I(3)-R antagonist, partially attenuated responses to IAA-RP. Taken together, these data support a role for IAA-RP in modulating synaptic transmission in the hippocampus through activation of I-Rs.


Assuntos
Hipocampo/fisiologia , Imidazóis/farmacologia , Receptores de Imidazolinas/agonistas , Receptores de Imidazolinas/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Inibição Neural/fisiologia , Ribosemonofosfatos/farmacologia , Transmissão Sináptica/fisiologia , Animais , Hipocampo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Masculino , Inibição Neural/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica/efeitos dos fármacos
15.
Ann Oncol ; 22(3): 689-695, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20810546

RESUMO

BACKGROUND: The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy. PATIENTS AND METHODS: Thirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles. RESULTS: Median age was 63 years (range, 37-82 years). Median number of prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression. CONCLUSION: Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Pirazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Bortezomib , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Zona Marginal Tipo Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Recidiva , Falha de Tratamento , Resultado do Tratamento
16.
Eur J Health Econ ; 22(9): 1349-1363, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34019220

RESUMO

OBJECTIVES: To assess the cost-effectiveness (CE) of transcatheter aortic valve implantation (TAVI) in Italy, considering patient groups with different surgical risk. METHODS: A Markov model with a 1-month cycle length, comprising eight different health states, defined by the New York Heart Association functional classes (NYHA I-IV), with and without stroke plus death, was used to estimate the CE of TAVI for intermediate-, high-risk and inoperable patients considering surgical aortic valve replacement or medical treatment as comparators according to the patient group. The Italian National Health System perspective and 15-year time horizon were considered. In the base-case analysis, effectiveness data were retrieved from published efficacy data and total direct costs (euros) were estimated from national tariffs. A scenario analysis considering a micro-costing approach to estimate procedural costs was also considered. The incremental cost-effectiveness ratio (ICER) was expressed both in terms of costs per life years gained (LYG) and costs per quality adjusted life years (QALY). All outcomes and costs were discounted at 3% per annum. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess robustness of results. RESULTS: Over a 15-year time horizon, the higher acquisition costs for TAVI were partially offset in all risk groups because of its effectiveness and safety profile. ICERs were €8338/QALY, €11,209/QALY and €10,133/QALY, respectively, for intermediate-, high-risk and inoperable patients. ICER values were slightly higher in the scenario analysis. PSA suggested consistency of results. CONCLUSIONS: TAVI would be considered cost-effective at frequently cited willingness-to-pay thresholds; further studies could clarify the CE of TAVI in real-life scenarios.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/cirurgia , Análise Custo-Benefício , Humanos , Itália , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
18.
Ann Oncol ; 20(8): 1344-51, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19468030

RESUMO

BACKGROUND: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. PATIENTS AND METHODS: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. RESULTS: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). CONCLUSIONS: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Adulto , Idoso , Amenorreia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/cirurgia , Receptores de Estrogênio/biossíntese , Proteínas Recombinantes , Transplante de Células-Tronco , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do Tratamento
19.
Ann Oncol ; 20(12): 1993-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19570964

RESUMO

BACKGROUND: Primary breast lymphoma (PBL) of low-grade histology is a rare disease. This multicentric retrospective study was carried out to determine clinical features, prognosis and relapse. PATIENTS AND METHODS: Patients with histologically proven, previously untreated follicular or marginal-zone PBL (MZL PBL) diagnosed from 1980 to 2003 were included in the study. Major end points were progression-free survival (PFS), overall survival (OS) and potential prognostic factors. RESULTS: We collected data on 60 cases of PBL [36 follicular and 24 marginal-zone lymphoma (MZL)]. Stage was I(E) or II(E) in 57 patients and IVE in three patients due to bilateral breast involvement. Surgery, chemotherapy and radiotherapy (RT), alone or in combination, were used as first-line treatments in 67%, 42% and 52% of patients, respectively. Overall response rate was 98%, with a 93% complete response rate. Five-year PFS were 56% for MZL and 49% for follicular PBL (P = 0.62). Relapses were mostly in distant sites (18 of 23 cases); no patients relapsed within RT fields. CONCLUSIONS: Our data showed an indolent behaviour of MZL PBL, comparable to other primary extranodal MZL. Conversely, patients with follicular PBL had inferior PFS and OS when compared with limited-stage nodal follicular non-Hodgkin's lymphomas, suggesting an adverse prognostic role of primary breast localisation in this histological subgroup.


Assuntos
Neoplasias da Mama Masculina/patologia , Neoplasias da Mama/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/terapia , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Masculino , Prognóstico , Resultado do Tratamento
20.
Hematol Oncol ; 27(3): 154-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19274614

RESUMO

Mantle cell lymphoma (MCL) has a poor prognosis with often short and incomplete remissions. We aimed to test the efficacy and tolerability of gemcitabine in treating MCL. Gemcitabine was given in doses of 1000 mg/m(2) as a 30 min infusion on days 1 and 8 of each 3 week cycle for a maximum of nine cycles. Eighteen patients with a median age of 70 years were recruited. MCL was newly diagnosed in half of patients and relapsed in the remainder. Fifteen patients had Ann Arbor stage IV. The best-recorded responses were 1 CR (complete remission), 4 PRs (partial responses), 8 SDs (stable diseases) and 4 PDs (diseases progression). The response rate (RR) (CR + PR) was 5 (28%; 95% confidence interval: 7.1, 48.5). The patient achieving a CR had stage IV disease. Most haematological adverse events occurred during the first chemotherapy cycle. Three patients developed non-haematological serious adverse events: dyspnea, glomerular microangiopathy with haemolytic uremic syndrome (HUS) and hyperglycaemia. The median time-to-progression and treatment response duration (TRD) was 8.0 (95% confidence interval: 5.5, 9.3) and 10.6 (95% confidence interval: 5.5, 10.9) months, respectively. We conclude that Gemcitabine is well tolerated, moderately active and can induce disease stabilization in patients with MCL.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Gencitabina
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