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1.
Eur J Pediatr ; 182(2): 957-964, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36459226

RESUMO

During the COVID-19 pandemic, children and adolescents with psychiatric disorders experienced an exacerbation of their symptoms with more access to the emergency department (ED). However, little is known about the experience of somatic symptom disorders (SSDs) during the COVID-19 pandemic in children. Therefore, we aimed to compare the rates of pediatric ED admissions for SSDs before and during the COVID-19 pandemic and to understand whether the relative risk of ED admissions for SSDs changed between the two periods. We retrospectively enrolled all children between 4 and 14 years admitted for SSDs in the pediatric ED of Santobono-Pausilipon Hospital, Naples, Italy, from March 11th, 2020, to March 11th, 2021 (pandemic period), and in the same time period of the previous year (pre-pandemic period). We identified 205/95,743 (0,21%) children with SSDs presenting in ED in the pre-pandemic year and 160/40,165 (0,39%) in the pandemic year (p < 0.05). Considering the accesses for age, we observed a relative decrease of the accesses for SSDs over 12 years old (IRR 0,59; CI 0,39-0,88), while we found no differences under 12 years old (IRR 0,87; CI 0,68-1,10).   Conclusion: In this study, we found that despite the massive decrease in pediatric admissions due to the COVID-19 pandemic, somatic symptom disorders' admissions to the pediatric ED increased, suggesting an impact of the pandemic also on pediatric psychiatric disorders. What is Known: • During the COVID -19 pandemic, children and adolescents with a psychiatric disorder experienced exacerbation of their symptoms with more accesses in Emergency Department. What is New: • We found that despite the massive decrease of the pediatric admissions due to the COVID-19 pandemic, somatic symptom disorders admissions in healthy children to the pediatric Emergency Department increased ,suggesting an impact of the pandemic also on the pediatric psychiatric disorders.


Assuntos
COVID-19 , Serviços Médicos de Emergência , Sintomas Inexplicáveis , Transtornos Mentais , Adolescente , Criança , Humanos , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Serviço Hospitalar de Emergência , Transtornos Mentais/epidemiologia
3.
Int J Neural Syst ; 30(8): 2050040, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727317

RESUMO

Machine learning (ML) systems are affected by a pervasive lack of transparency. The eXplainable Artificial Intelligence (XAI) research area addresses this problem and the related issue of explaining the behavior of ML systems in terms that are understandable to human beings. In many explanation of XAI approaches, the output of ML systems are explained in terms of low-level features of their inputs. However, these approaches leave a substantive explanatory burden with human users, insofar as the latter are required to map low-level properties into more salient and readily understandable parts of the input. To alleviate this cognitive burden, an alternative model-agnostic framework is proposed here. This framework is instantiated to address explanation problems in the context of ML image classification systems, without relying on pixel relevance maps and other low-level features of the input. More specifically, one obtains sets of middle-level properties of classification inputs that are perceptually salient by applying sparse dictionary learning techniques. These middle-level properties are used as building blocks for explanations of image classifications. The achieved explanations are parsimonious, for their reliance on a limited set of middle-level image properties. And they can be contrastive, because the set of middle-level image properties can be used to explain why the system advanced the proposed classification over other antagonist classifications. In view of its model-agnostic character, the proposed framework is adaptable to a variety of other ML systems and explanation problems.


Assuntos
Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Modelos Teóricos , Dicionários como Assunto , Humanos
4.
Neurobiol Learn Mem ; 161: 63-71, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30898692

RESUMO

The ability to learn that a stimulus no longer signals danger is known as extinction. A major characteristic of extinction is that it is context-dependent, which means that fear reduction only occurs in the same context as extinction training. In other contexts, there is re-emergence of fear, known as contextual renewal. The ability to properly extinguish fear memories and generalize safety associations to multiple contexts provides therapeutic potential, but little is known about the specific neural pathways that mediate fear renewal and extinction generalization. The ventral hippocampus (VH) is thought to provide a contextual gating mechanism that determines whether fear or safety is expressed in particular contexts through its projections to areas of the fear circuit, including the infralimbic (IL) and prelimbic (PL) cortices. Moreover, VH principal cells fire in large, overlapping regions of the environment, a characteristic that is ideal to support generalization; yet it is unclear how different projection cells mediate this process. Using a pathway-specific (intersectional) chemogenetic approach, we demonstrate that selective activation of VH cells projecting to PL attenuates fear renewal without affecting fear expression. These results have implications for anxiety disorders since they uncover a neural pathway associated with extinction generalization.


Assuntos
Extinção Psicológica/fisiologia , Medo/fisiologia , Giro do Cíngulo/fisiologia , Hipocampo/fisiologia , Rememoração Mental/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Comportamento Animal/fisiologia , Técnicas Genéticas , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Data Brief ; 19: 1530-1536, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30229025

RESUMO

Oxygen absorption measurements in continuous regard active multilayer films with different layouts, all incorporating a PET/Oxygen scavenger (OS) layer, operating as active O2 barrier, inserted between two PET inert layers, acting as passive O2 barrier. The data set is related to "Transport properties of multilayer active PET films with different layers configuration" by Apicella et al. (2018) [1]. A set of four multilayer films, with different relative thickness of the active and inert layers, was produced using a laboratory scale co-extrusion cast-film equipment and was analyzed in terms of oxygen scavenging performance. Single layer active and inert layers were also produced for comparison. The results have shown a longer exhaustion time for all the active multilayer films, respect to the active monolayer one. Moreover, at constant thickness of the active layer, the exhaustion time increases by increasing the thickness of the inert layers, whereas, at constant thickness of the inert layers, the residual oxygen concentration decreases by increasing the thickness of the active layer.

7.
J Biol Regul Homeost Agents ; 29(4): 991-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26753666

RESUMO

Dental pulp stem cells (DPSCs) are stem cells found in the dental pulp. The ability of DPSCs to differentiate towards odontoblastic and osteoblastic phenotype was reported first in the literature, then in the following years, numerous studies on odontogenesis were carried out, starting from mesenchymal stem cells isolated from tissues of dental and oral origin. The aim of this research was to evaluate the behaviour of DPSCs grown on silicon nanoporous and mesoporous matrices and differentiated towards the osteogenic phenotype, but also to investigate the use of DPSCs in pilot studies focused on the biological compatibility of innovative dental biomaterials. Twenty-eight silicon samples were created with standardized procedures. These scaffolds were divided into samples made of silicon bulk, nanoporous silicon, mesoporous silicon, nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH), nanoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene, mesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS) and methanol (MeOH) andmesoporous silicon functionalized with (3-Aminopropyl) Trimethoxysilane (APTMS)/toluene. DPSC proliferation on the tested silicon scaffolds was analyzed at 3 and 5 days. The assay showed that DPSCs proliferated better on mesoporous scaffolds functionalized with APTMS/toluene compared to a silicon one. These results show that the functionalization of silicon scaffold with APTMS/toluene supports the growth of DPSCs and could be used for future applications in tissue engineering.


Assuntos
Polpa Dentária/citologia , Células-Tronco/citologia , Alicerces Teciduais , Adulto , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Nanoestruturas , Porosidade , Silício , Engenharia Tecidual
8.
Ann Ig ; 20(3): 211-21, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-18693399

RESUMO

Our study was undertaken to determine how the use of care pathways in hospital affected the quality of the care of the patients. We performed a cluster-randomized trial. The use of diagnostic procedures and of medical treatments was more appropriate in the care pathways group, as well as the discharge process. As a consequence the outcomes indicators adopted in our study showed better performances in the care pathways group when compared to the usual care group. Our study added evidences on the value of clinical pathways that can be effectively used to improve the quality of hospital care. The use of CP helped to create a constant dialogue within the clinicians, ensured that important areas of treatment were not overlooked and unnecessary delays were prevented by timely interventions. We think that our results are reliable because we adopted a cluster-randomized controlled trial design that is widely accepted as the most reliable method of determining effectiveness of complex interventions in healthcare.


Assuntos
Procedimentos Clínicos/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Prospectivos
9.
G Chir ; 28(3): 99-102, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17419906

RESUMO

English version We present a case of bulky schwannoma arising from the brachial plexus treated by a new surgical device. A 38-year-old man presented with a slow-growing left-sided supraclavicular mass and complained paresthesia of the third and forth fingers of the hand and forearm weakness. Physical examination revealed Tinel's sign. A CT-scan revealed a solid mass situated in the left profound supraclavicular fossa. The tumour was resected with the utilization of bipolar vessel sealing system (Ligasure Precise). This device is very useful in sutureless removal of masses localized in deep supraclavicular fossa. During the operation, care was taken to preserve the nerve function.


Assuntos
Plexo Braquial , Eletrocirurgia , Neurilemoma/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Adulto , Eletrocirurgia/instrumentação , Humanos , Masculino
10.
Dent Mater ; 22(11): 1035-44, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16406084

RESUMO

OBJECTIVE: The present study aimed at evaluating different restoring configurations of a crownless maxillary central incisor, in order to compare the biomechanical behavior of the restored tooth with that of a sound tooth. MATERIALS AND METHODS: A 3D FE model of a maxillary central incisor is presented. An arbitrary static force of 10 N was applied with an angulation of 125 degrees to the tooth longitudinal axis at level of the palatal surface of the crown. Different material configurations were tested: composite, syntered alumina, feldspathic ceramic endocrowns and glass post resorations with syntered alumina and feldspathic ceramic crown. RESULTS: High modulus materials used for the restoration strongly alter the natural biomechanical behavior of the tooth. Critical areas of high stress concentration are the restoration-cement-dentin interface both in the root canal and on the buccal and lingual aspects of the tooth-restoration interface. Materials with mechanical properties underposable to that of dentin or enamel improve the biomechanical behavior of the restored tooth reducing the areas of high stress concentration. SIGNIFICANCE: The use of endocrown restorations present the advantage of reducing the interfaces of the restorative system. The choice of the restorative materials should be carefully evaluated. Materials with mechanical properties similar to those of sound teeth improve the reliability of the restoartive system.


Assuntos
Coroas , Materiais Dentários/química , Análise de Elementos Finitos , Incisivo/fisiologia , Óxido de Alumínio/química , Silicatos de Alumínio/química , Fenômenos Biomecânicos , Cerâmica/química , Resinas Compostas/química , Simulação por Computador , Esmalte Dentário/fisiologia , Porcelana Dentária/química , Cavidade Pulpar/fisiologia , Análise do Estresse Dentário , Dentina/fisiologia , Elasticidade , Vidro/química , Humanos , Imageamento Tridimensional , Maxila , Modelos Biológicos , Técnica para Retentor Intrarradicular/instrumentação , Compostos de Potássio/química , Cimentos de Resina/química , Estresse Mecânico
11.
Anticancer Res ; 23(5b): 4101-3, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14666608

RESUMO

Canalicular adenoma is an uncommon benign neoplasm that occurs almost exclusively in the upper lip and, very rarely, in other sites. We describe a case arising in the left parotid gland as a firm, painful mass, in order to underline morphological and immunohistochemical findings, particularly in relation to differential diagnosis with low-grade carcinomas of the salivary glands.


Assuntos
Adenoma/patologia , Neoplasias Parotídeas/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
12.
Clin Exp Immunol ; 129(3): 502-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12197892

RESUMO

Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by defect of T- and B-cell immunity. In many cases of autosomal recessive SCID, thus far described, the molecular alteration involves genes encoding for molecules that participate in the signal transduction. We report on a patient affected by a combined immunodeficiency, characterized by severe T-cell functional impairment, in spite of a close to normal number of circulating mature type T and B cells. NK cells were absent. Associated with the immunodeficiency, this patient also showed short stature characterized by very low growth velocity, delayed bone age and absence of increase of the plasma levels of Insulin growth factor-I (IGF-I) after growth hormone (GH) in vivo stimulation indicating peripheral hyporesponsiveness to GH. Evaluation of the protein tyrosine phosphorylation events occurring following either T-cell receptor (TCR) or GH receptor (GHR) triggering revealed striking abnormalities. No molecular alteration of GHR gene was found, thus suggesting the presence of postreceptorial blockage. Mutational screening and expression analysis failed to reveal any molecular alteration of JAK2 and STAT 5 A/B genes thus ruling out the involvement of these genes in the pathogenesis of this form of SCID. Mutational analysis of IL2Rgamma chain gene revealed the presence of a L183S missense mutation, thus indicating an atypical and a more complex clinical presentation of this X-linked form of SCID. At our knowledge, this is the first report on the GH hyporesponsiveness in this disease.


Assuntos
Hormônio do Crescimento Humano , Proteínas do Leite , Proteínas Proto-Oncogênicas , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologia , Antígenos de Diferenciação de Linfócitos T/análise , Estatura , Células Cultivadas , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Seguimentos , Ligação Genética , Hormônio do Crescimento Humano/farmacologia , Humanos , Lactente , Subunidade gama Comum de Receptores de Interleucina , Janus Quinase 2 , Ativação Linfocitária , Masculino , Linhagem , Fenótipo , Fosforilação , Proteínas Tirosina Quinases/genética , RNA Mensageiro/biossíntese , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Interleucina-7/genética , Receptores da Somatotropina/análise , Receptores da Somatotropina/metabolismo , Fator de Transcrição STAT5 , Imunodeficiência Combinada Severa/genética , Linfócitos T/imunologia , Transativadores/biossíntese , Transativadores/genética , Cromossomo X
13.
Br J Cancer ; 86(9): 1501-9, 2002 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-11986787

RESUMO

Numerous studies demonstrate that the chemopreventive effect of non-steroidal anti-inflammatory drugs on colon cancer is mediated through inhibition of cell growth and induction of apoptosis. For these effects non-steroidal anti-inflammatory drugs have been recently employed as sensitising agents in chemotherapy. We have shown previously that treatments with aspirin and NS-398, a cyclo-oxygenase-2 selective inhibitor, affect proliferation, differentiation and apoptosis of the human colon adenocarcinoma Caco-2 cells. In the present study, we have evaluated the effects of aspirin and NS-398 non-steroidal anti-inflammatory drugs on sensitivity of Caco-2 cells to irinotecan (CPT 11) and etoposide (Vp-16) topoisomerase poisons. We find that aspirin co-treatment is able to prevent anticancer drug-induced toxicity, whereas NS-398 co-treatment poorly affects anticancer drug-induced apoptosis. These effects correlate with the different ability of aspirin and NS-398 to interfere with cell cycle during anticancer drug co-treatment. Furthermore, aspirin treatment is associated with an increase in bcl-2 expression, which persists in the presence of the anticancer drugs. Our data indicate that aspirin, but not NS-398, determines a cell cycle arrest associated with death suppression. This provides a plausible mechanism for the inhibition of apoptosis and increase in survival observed in anticancer drug and aspirin co-treatment.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Aspirina/farmacologia , Inibidores Enzimáticos/farmacologia , Nitrobenzenos/farmacologia , Sulfonamidas/farmacologia , Inibidores da Topoisomerase , Células CACO-2 , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Sobrevivência Celular , Etoposídeo/farmacologia , Humanos , Irinotecano
14.
J Biomech ; 34(10): 1269-77, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11522306

RESUMO

The combination of diverse materials and complex geometry makes stress distribution analysis in teeth very complicated. Simulation in a computerized model might enable a study of the simultaneous interaction of the many variables. A 3D solid model of a human maxillary premolar was prepared and exported into a 3D-finite element model (FEM). Additionally, a generic class II MOD cavity preparation and restoration was simulated in the FEM model by a proper choice of the mesh volumes. A validation procedure of the FEM model was executed based on a comparison of theoretical calculations and experimental data. Different rigidities were assigned to the adhesive system and restorative materials. Two different stress conditions were simulated: (a) stresses arising from the polymerization shrinkage and (b) stresses resulting from shrinkage stress in combination with vertical occlusal loading. Three different cases were analyzed: a sound tooth, a tooth with a class II MOD cavity, adhesively restored with a high (25 GPa) and one with a low (12.5GPa) elastic modulus composite. The cusp movements induced by polymerization stress and (over)-functional occlusal loading were evaluated. While cusp displacement was higher for the more rigid composites due to the pre-stressing from polymerization shrinkage, cusp movements turned out to be lower for the more flexible composites in case the restored tooth which was stressed by the occlusal loading. This preliminary study by 3D FEA on adhesively restored teeth with a class II MOD cavity indicated that Young's modulus values of the restorative materials play an essential role in the success of the restoration. Premature failure due to stresses arising from polymerization shrinkage and occlusal loading can be prevented by proper selection and combination of materials.


Assuntos
Dente Pré-Molar/fisiologia , Restauração Dentária Permanente/normas , Análise do Estresse Dentário/métodos , Resinas Compostas/normas , Resinas Compostas/uso terapêutico , Colagem Dentária/métodos , Colagem Dentária/normas , Materiais Dentários , Restauração Dentária Permanente/métodos , Elasticidade , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Teste de Materiais , Modelos Dentários , Movimento , Resistência à Tração
15.
Psychiatr Serv ; 52(3): 378-80, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11239109

RESUMO

Adherence to recommended services is essential for long-term effectiveness of ambulatory treatment programs, but factors associated with such adherence are not securely established. We evaluated attendance at 896 scheduled psychiatric clinic visits for 62 patients at a major psychiatric teaching hospital. Visit adherence was found to be significantly higher among patients in an acute stage of illness, those with a personality disorder, those with a post-high-school education, and those living alone. Adherence was also higher when visits were routinely scheduled, when the intervisit interval was shorter, and when the visit entailed psychotherapy rather than pharmacotherapy.


Assuntos
Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Ambulatório Hospitalar/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adulto , Feminino , Hospitais Psiquiátricos , Hospitais de Ensino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
16.
Oncogene ; 19(48): 5517-24, 2000 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-11114729

RESUMO

Nonsteroidal anti-inflammatory drugs reduce the risk of colon cancer and this effect is mediated in part through inhibition of type 2 prostaglandin endoperoxide synthase/ cyclo-oxygenase (COX-2). In the present study, we demonstrate that COX-2 expression and PGE2 synthesis are up-regulated by an IGF-II/IGF-I receptor autocrine pathway in Caco-2 colon carcinoma cells. COX-2 mRNA and PGE2 levels are higher in proliferating cells compared with post-confluent differentiated cells and in cells that constitutively overexpress IGF-II. Up-regulation of COX-2 expression by IGF-II is mediated through activation of IGF-I receptor because: (i) treatment of Caco-2 cells with a blocking antibody to the IGF-I receptor inhibits COX-2 mRNA expression; (ii) transfection of Caco-2 cells with a dominant negative IGF-I receptor reduces COX-2 expression and activity. Also, the blockade of the PI3-kinase, that mediates the proliferative effect of IGF-I receptor in Caco-2 cells, inhibits IGF-II-dependent COX-2 up-regulation and PGE2 synthesis. Moreover, COX-2 expression and activity inversely correlate with the increase of apoptosis in parental, IGF-II and dominant-negative IGF-I receptor transfected cells. This study suggests that induction of proliferation and tumor progression of colon cancer cells by the IGF-II/IGF-I receptor pathway may depend on the activation of COX-2-related events.


Assuntos
Células CACO-2/metabolismo , Dinoprostona/biossíntese , Fator de Crescimento Insulin-Like II/fisiologia , Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , RNA Mensageiro/biossíntese , Receptor IGF Tipo 1/fisiologia , Anti-Inflamatórios não Esteroides/farmacologia , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Células CACO-2/enzimologia , Divisão Celular/fisiologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Progressão da Doença , Humanos , Fator de Crescimento Insulin-Like II/antagonistas & inibidores , Fator de Crescimento Insulin-Like II/biossíntese , Isoenzimas/genética , Isoenzimas/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Membrana , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Nitrobenzenos/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , RNA Mensageiro/genética , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Transdução de Sinais/fisiologia , Sulfonamidas/farmacologia , Transfecção , Regulação para Cima/fisiologia
17.
Minerva Stomatol ; 49(7-8): 389-92, 2000.
Artigo em Italiano | MEDLINE | ID: mdl-11234691

RESUMO

A case of angioleiomyoma localized at the level of the soft palate is reported. The 31-year-old patient presented a non-pathognomonic clinical picture and the anamnestic finding of the relatively slow growth of the neoformation raised problems of differential diagnosis in relation to benign growth and lesion of a non-neoplastic nature. The differential diagnosis was only obtained with histological examination of biopsy material.


Assuntos
Angiomioma/patologia , Neoplasias Palatinas/patologia , Adulto , Humanos , Masculino
18.
J Mater Sci Mater Med ; 11(4): 201-6, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15348032

RESUMO

Carbon fiber posts (CFP) are widely used in the restoration of endodontically treated teeth to enhance the mechanical behavior in spite of metallic posts and to prevent vertical fractures of the tooth under chewing loads. The post is cemented inside the canal lumen using polymer resins with Young's modulus lower than dentine. In this conditions the stress concentration is located at the post-cement interface and in the cement bulk itself, preserving radicular dentine from dangerous stress accumulation. The mechanical resistance of CFP posts cemented in human dentine was evaluated by the means of mechanical pull-out tests assisted by the finite element analysis. The average bond strength and the critical stress values of the CHP-cement interface were 25 MPa and 50 MPa respectively.

19.
Breast Cancer Res Treat ; 56(3): 239-52, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10573115

RESUMO

PURPOSE: Both cisplatin and epirubicin have been shown to enhance the antitumor activity of paclitaxel in vitro. Weekly administration could result in a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at determining the MTDs of epirubicin and paclitaxel given weekly with a fixed dose of cisplatin. PATIENTS AND METHODS: Sixty-three breast cancer patients with advanced disease (24 locally advanced and 39 metastatic), who had not received prior chemotherapy (except adjuvant), received weekly cisplatin (CDDP) doses of 30 mg/m2 together with escalating doses of paclitaxel (PTX) and epirubicin (EPI) for a minimum of six cycles. The dose escalation was stopped if DLT occurred during the first six treatment cycles in > 33% of patients of a given cohort. RESULTS: Nine different dose levels were tested, for a total of 506 weekly cycles delivered. G-CSF support on days 3-5 of each week was also given in the last four cohorts (24 patients). An overall 11 patients showed DLT in the first six cycles. EPI and PTX doses up to 40 and 85 mg/m2/week, respectively, were safely delivered without G-CSF support. However, the actually delivered mean dose intensity was only 64% in this cohort. Therefore, the dose escalation continued with the addition of filgrastim from day 3 to day 5 each week. Doses of EPI and PTX up to 50 and 120 mg/m2/week were administered without observing DLT in the first six cycles in more than one third of the patients enrolled. No toxic deaths were observed. Only two patients had to be hospitalized because of sepsis. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 25, 9, and 16 patients, respectively. Alopecia was almost universal. Other nonhematologic toxicities were generally mild, being of grade 3-4 in only eight patients (fatigue and loss of appetite in two cases, diarrhoea in four cases, peripheral neuropathy and mucositis in one case). Fifteen complete and 37 partial responses have been registered for an 82% (95% CI = 71-91) overall clinical response rate (ORR). Eight complete and 14 partial responses occurred in the 24 patients with locally advanced disease, for a 92% (95% CI = 73-99) ORR, as compared to seven complete and 23 partial responses in the 39 women with metastatic disease, 77% (95% CI = 61-89). A clear dose-response relationship was not observed, since an overall response rate of at least 70% was achieved at all dose levels. However, the ORR increased to 92% in the last four cohorts which included patients who received higher doses of EPI and PTX with G-CSF support. All of the 24 patients with locally advanced disease underwent modified radical mastectomy with axillary dissection. Three of them showed no invasive cancer on pathologic examination, and in another five patients a tumor smaller than 1 cm was found in the surgical specimen of the breast. At a nine-month median follow-up (range 2-14), 11 patients have progressed and three have died. Twenty-three out of 24 patients who underwent surgery are still free from progression. The one-year projected progression-free survival is 77% for the whole population. CONCLUSIONS: The CDDP/EPI/PTX weekly administration is a well tolerated and very effective approach in advanced breast cancer patients. Full doses of all the three drugs can be delivered even in absence of G-CSF support. A very impressive increment of the dose-intensity can be obtained, however, by adding filgrastim. A phase II study is under way to better define the therapeutic efficacy of this regimen in patients with advanced breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Sinergismo Farmacológico , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Infusões Intravenosas , Injeções Intravenosas , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Proteínas Recombinantes
20.
Ann Oncol ; 10(3): 355-8, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10355583

RESUMO

PURPOSE: Paclitaxel (PTX) and topotecan (TPT) have shown promising antitumor activity in both ovarian cancer (OC) and small-cell lung cancer (SCLC) patients. This phase I study was aimed at determining the maximum tolerable dose (MTD) of TPT given weekly over 30 min in combination with fixed doses of cisplatin (CDDP) and (PTX), and with G-CSF support. PATIENTS AND METHODS: Forty-four patients with OC (19) or SCLC (25), either chemo-naïve (20) or pretreated (24) received CDDP 40 mg/m2, PTX 85 mg/m2 (one-hour infusion) and escalating TPT doses (starting from 0.75 mg/m2) in a 30-min infusion in weekly administration. Filgrastim 5 mg/kg was administered on days 3 to 5 of each week. RESULTS: Eight different dose levels were tested for a total of 295 delivered cycles. The dose escalation was interrupted at the TPT dose of 2.50 mg/m2. No toxic deaths occurred in this study. Grade 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 15 patients (36 cycles), seven patients (15 cycles), and four patients (five cycles), respectively. Severe vomiting and diarrhoea occurred in seven and four patients. Peripheral neuropathy was recorded in 11 patients (42 cycles), but it was never severe. An overall 11 of 19 (58%) OC and 11 of 25 (44%) SCLC patients obtained objective responses. Eight patients showed complete responses (three OC and three SCLC). Among the 20 chemo-naïve patients, 9 of 11 (82%) OC and seven of nine (78%) SCLC responded. CONCLUSIONS: The CDDP/TPT/PTX weekly administration with filgrastim support represents a well-tolerated and active therapeutic approach in both chemo-naïve and pretreated OC and SCLC patients. A weekly dose of TPT of 2.25 mg/m2 is recommended for the phase II study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Prognóstico , Topotecan/administração & dosagem , Resultado do Tratamento
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