Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Dermatomiosite/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Síndromes Paraneoplásicas , Idoso , Carcinoma de Células Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , MasculinoRESUMO
PURPOSE OF REVIEW: This review aims to summarize the current knowledge on the genetic background of dilated cardiomyopathy (DCM), with particular attention to the genotype-phenotype correlations and the possible implications for clinical management. RECENT FINDINGS: Next generation sequencing (NGS) has led to the identification of an increasing number of genes and mutations responsible for DCM. This genetic variability is probably related to the extreme heterogeneity of disease manifestation. Important findings have associated mutations of Lamin A/C (LMNA) and Filamin C (FLNC) to poor prognosis and the propensity to cause an arrhythmic phenotype, respectively. However, a deeper understanding of the genotype-phenotype correlation is necessary, because it could have several implications for the clinical management of the patients. Furthermore, the correct interpretation of pathogenicity of mutations and the clinical impact of genetic testing in DCM patients still represent important fields to be implemented. A pathogenic gene mutation can be identified in almost 40% of DCM patients. The recent discoveries and future research in the field of genotype-phenotype correlation may lead to a more personalized management of the mutation carriers towards the application of precision medicine in DCM.
Assuntos
Cardiomiopatia Dilatada/genética , Mutação , Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidade , Cardiomiopatia Dilatada/cirurgia , Morte Súbita Cardíaca/etiologia , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Prognóstico , Medição de Risco , Fatores de RiscoAssuntos
Antibacterianos/efeitos adversos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , beta-Lactamas/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/patologia , Oxacilina/efeitos adversos , Oxacilina/uso terapêutico , Pele/patologia , Doença de Still de Início Tardio/tratamento farmacológico , beta-Lactamas/uso terapêuticoRESUMO
OBJECTIVES: Important adjustments in the autonomic nervous system occur during sleep. Bradycardia, due to increased vagal tone, and hypotension, caused by reduction of sympathetic activity, may occur during non rapid eye movement (REM) sleep (NREM). Increased sympathetic activity, causing increased heart rate, is conversely a feature of phasic REM sleep. During REM sleep, sinus arrests and atrioventricular (AV) blocks unrelated to apnea or hypopnea have been described. These arrhythmias are very rare and only a few cases have been reported in the literature. PATIENTS/METHODS: Following an ECG performed for other reasons, two patients with no history of sleep complaints nor symptoms of heart failure or heart attack were referred to our center for nocturnal brady-arrhythmias. RESULTS: 24h ECG Holter recorded several episodes of brady-arrhythmia with sinus arrest in the first patients and brady-arrhythmias with complete AV block in the second patient. In both patients, episodes of brady-arrhythmia were prevalent in the second part of the night. Nocturnal polysomnography (PSG) demonstrated that episodes occurred only during REM sleep, particularly during phasic events. Treatment with pacemaker was considered only for the patient with complete AV blocks. CONCLUSIONS: These types of brady-arrhythmias are usually detected accidentally due to their lack of symptoms. It has been suggested that in some patients they may lead to sudden unexpected death. Thus, the identification of predisposing factors is mandatory in order to prevent potentially dangerous arrhythmic events.
Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Bradicardia/diagnóstico , Bradicardia/terapia , Estimulação Cardíaca Artificial , Sono REM , Adulto , Doenças do Sistema Nervoso Autônomo/complicações , Bradicardia/etiologia , Ritmo Circadiano , Eletrocardiografia Ambulatorial , Humanos , Masculino , Polissonografia , Parada Sinusal Cardíaca/diagnóstico , Parada Sinusal Cardíaca/etiologia , Parada Sinusal Cardíaca/terapia , Adulto JovemRESUMO
Large vessel involvement by skeletal and soft tissue sarcomas of the extremities does not change the modern limb sparing surgery for those neoplasms. An arterial and, if the vein is open, a venous bypass should always be offered to any patient young or old, with high or low grade sarcoma, because preserving the limb permits quicker rehabilitation, which is particularly useful in the case of a short life expectancy. In 650 cases of skeletal sarcomas, 10 arterial (1.5%) and four venous bypasses were done, all with autologous veins but one in PTFE; we had no problems except a silent arterial occlusion. Of 1000 patients with soft tissue sarcomas, 32 (3%) had vessel involvement permitting limb sparing surgery. The arterial bypass, which is the limb-saving operation, was performed 16 times with a PTFE with one early occlusion and four cases of prosthesis infection, with two amputations despite redo operation with an autologous vein. The more recent 16 cases were, therefore, always done with biological vessel substitution--autologous vein or tissue bank vessel--with only one infection that healed without operation and one case of homograft rupture followed by amputation. Since 1999 in all 13 resected cases with an open vein, we did the arterial and the venous bypass (twice PTFE, six autologous vein, and five bank vessel) with the aim of avoiding postoperative venous hypertension, but only four of the venous bypasses remained open. Venous bypasses are a harmless, but still experimental, procedure.
Assuntos
Vasos Sanguíneos/transplante , Neoplasias Ósseas/cirurgia , Sarcoma/cirurgia , Transplante Homólogo/métodos , Artérias/cirurgia , Neoplasias Ósseas/irrigação sanguínea , Humanos , Estudos Retrospectivos , Sarcoma/irrigação sanguínea , Resultado do Tratamento , Veias/cirurgiaRESUMO
BACKGROUND: Giant cell tumor of bone (GCT) is a benign tumor with a significant tendency to recur locally and rarely to produce pulmonary metastases. It is characterized by the presence of multinucleated osteoclast-like giant cells together with mononuclear spindle-shaped cells. Few prognostic markers have been reported to predict the clinical outcome of GCT patients, so is very important to find the factor that can be implicated in its potential aggressiveness. PATIENTS AND METHODS: Different groups of GCT patients were selected for this study, including patients without evidence of disease and patients who recurred locally or with lung metastasis. The total of 92 tumor samples also included the specimens of the local recurrences and the lung metastases. By using immunohistochemistry and real-time quantitative polymerase chain reaction techniques, the genetic and proteic analyses were performed on the urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and its inhibitor (PAI-1), which have been described to be frequently implicated in the process of degradation of the extracellular matrix during the metastatic process. Interleukin-6 (IL-6), a cytokine released by GCT cells, which stimulates resorption of bone, was also analyzed. RESULTS: IL-6, u-PA, u-PAR and PAI 1 genes were found amplified, respectively, in 7%, 5%, 8% and 12% of total cases (92). In particular, the percentages of amplified genes were higher in the GCT cells that gave rise to metastases (12 cases) and in the samples of lung metastases (nine cases) compared with the disease-free group of patients (60 cases). CONCLUSIONS: These results suggest a possible association of these factors with a higher biological aggressiveness of GCT. Morever, it appears that increased expression of the IL-6, u-PA, u-PAR and PAI1 proteins might not depend on mutation of the corresponding genes.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Tumor de Células Gigantes do Osso/genética , Interleucina-6/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Receptores de Superfície Celular/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Reabsorção Óssea , Tumor de Células Gigantes do Osso/patologia , Humanos , Técnicas Imunoenzimáticas , Interleucina-6/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ativador de Plasminogênio Tipo Uroquinase/metabolismoAssuntos
Sarcoma/cirurgia , Academias e Institutos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Extremidades/cirurgia , Feminino , Humanos , Lactente , Itália , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Ortopedia , Estudos Retrospectivos , Sarcoma/terapia , Resultado do TratamentoRESUMO
The authors describe a variation in the method of vertebral hemi-resection used for the treatment of neoplasms that present a wide invasion of the vertebral canal. This is followed by a review of the literature on the subject.
Assuntos
Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Humanos , Laminectomia , Invasividade Neoplásica , Procedimentos de Cirurgia PlásticaRESUMO
A consecutive series of 57 patients treated by knee resection arthrodesis for malignant or aggressive tumor around the knee was reviewed. Infection was present only after repeated surgery for other complications, delayed union or non-union occurred in 50% of the cases that could be evaluated, but were still easy to manage. Fracture incidence was higher than expected (32.6%) even occurring after 10 years; this was difficult to deal with and it often led to failure. The best possible method of fixation is still being debated, but locked nail and allograft cementation is often advised. Several satisfactory functional results were however achieved when surgery was performed in young patients; final results can be less satisfactory when there is leg length discrepancy and poor acceptance on the part of the patient. In recent years this type of surgery has been limited to younger male patients (10 to 14 years of age) in whom extra-articular knee resection was required or when most of the quadriceps muscle must be removed.
Assuntos
Artrodese/métodos , Neoplasias Ósseas/cirurgia , Transplante Ósseo , Articulação do Joelho/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
A conjugate between the antitumor drug camptothecin and the polymeric drug-carrier poly[N-(2-hydroxypropyl)methacrylamide] was synthesized and fractionated. The conjugate samples, both fractionated and unfractionated, were characterized with a multi-detector SEC system using three on-line detectors: a multi-angle light scattering photometer, a viscometer, and a refractometer. The used mobile phase (DMF + 0.01 M LiBr + 0.05 M CH(3)COOH) derives from previous experience with similar conjugates. Narrow molar mass distribution fractions of the conjugate obtained by means of a semipreparative LC system were used to derive the coefficients of the Mark-Houwink-Sakurada relationship and to check the universal calibration of the SEC system. This study has demonstrated that the conjugate elutes according to the hydrodynamic volume. Thus, a conventional SEC method that uses only an on-line refractometer detector, commercially available narrow standards, and the universal calibration is adequate for the characterization of the molar mass distribution. Also the size and the conformation of the conjugate were studied by means of the gyration radius-molar mass power law.
Assuntos
Antineoplásicos/química , Camptotecina/química , Portadores de Fármacos/química , Portadores de Fármacos/isolamento & purificação , Ésteres/química , Metacrilatos/química , Polímeros/química , Antineoplásicos/isolamento & purificação , Calibragem , Camptotecina/isolamento & purificação , Ésteres/isolamento & purificação , Metacrilatos/isolamento & purificação , Estrutura Molecular , Polímeros/isolamento & purificaçãoRESUMO
Camptothecin (CPT) is a potent, antitumour drug acting mainly through inhibition of topoisomerase I during the S-phase of the cell cycle. Despite its impressive antitumour activity, clinical development was halted for unpredictable toxic events. Two soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers were synthesised to contain CPT (5 wt.% and 10 wt.%). CPT was covalently linked at its alpha-hydroxyl group to the polymers through a Gly-Phe-Leu-Gly- spacer. In-vitro, CPT-conjugates were fairly resistant to hydrolysis in plasma as in buffer at neutral pH (0.2-0. 4% free CPT/h), while elastase and cysteine-proteases were able to release the active drug. Plasma levels in mice after intravenous administration of CPT-conjugates confirmed the modest hydrolysis in plasma. Plasma levels were approximately 5-fold lower than those observed at the highest tolerated dose of CPT administered in classical vehicles. Biodistribution in HT29 human colon carcinoma bearing mice was carried out after i.v. injection of [3H]CPT-conjugate and free [3H]CPT. Radioactivity uptake in tumour was evident only after [3H]CPT-conjugate treatment. Repeated intravenous administration of CPT-conjugates to HT29-bearing mice gave more than 90% tumour inhibition, some complete tumour regressions and no toxic deaths. The improved pharmacological profile on HT29 human colon carcinoma xenografts of the first poly(HPMA)-CPT conjugates might be ascribed to their prolonged intra-tumour retention and sustained release of the active drug.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Autorradiografia , Soluções Tampão , Camptotecina/administração & dosagem , Preparações de Ação Retardada , Células HT29 , Humanos , Hidrólise , Injeções Intravenosas , Cinética , Metacrilatos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Polímeros , Distribuição Tecidual , Transplante HeterólogoRESUMO
At the present time breast cancer represents the primary reason of death caused by cancer amongst the female population of the western countries. Since the actuation of primary prevention programmes results impossible, the aim that must be considered primary is to attain a diagnosis of such tumour as precociously as possible. This research proposes to value the inclination of the female population of a District in Rome, of different classes of age, to have a mammography test in a state of spontaneous screening, in view of a next institution of a structured program of secondary prevention in the area of reference. The results have been examined with relation to the age limits considered as optimum for a correct application of this diagnostic methodology, in line with technical and epidemiological considerations.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Mamografia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Estudos de Coortes , Dieta , Feminino , Humanos , Menarca , Menopausa , Pessoa de Meia-Idade , Paridade , Gravidez , Fatores de Risco , Cidade de Roma/epidemiologiaRESUMO
We study the double excitation of surface modes at a metallic film that separates a uniaxial medium from an isotropic dielectric. We find that, for certain constitutive parameters of the structure, two normal modes can be associated to the film. It is found that the distance in the complex plane between the propagation constants of these modes can be considerably reduced by tuning conveniently film parameters, although the propagation constants are "reluctant" to coincide. We also show that a plane wave incident on the film from the crystal side can excite both modes simultaneously, without corrugating the surface or adding another layer. We obtain values of the film width for which the resonances appear at similar angles of incidence and show that these excitations are accompanied by an important increase of the power absorbed by the film and an enhancement of the fields at the two interfaces.
RESUMO
Deoligomerization of human tumor necrosis factor alpha (TNF), spiked with 125I-labeled form, was studied quantitatively using size-exclusion chromatography and off-line monitoring with a gamma-counter. A detailed investigation of the oligomeric state of TNF was carried out as a function of its own concentration (0.3-7500 nM referred to the subunit, M(r) 17,000) in the absence or in the presence of various amounts (10, 100, 1000 microM) of suramin, an inhibitor of TNF biological activity in vitro, which promotes TNF deoligomerization. The dependence of trimeric form content on total TNF concentration was modeled with a sequential dissociation process (trimer-->dimer-->monomer) assuming an identical dissociation constant for each step, Kd1 = 0.2 nM. This model was used as the simplest for data fitting although, generally, no chromatographic resolution of dimeric species could be obtained. Best fitting of all data could be achieved with a model including a conformational change of TNF trimer into a state more prone to deoligomerization (Kd2 = 400 nM), which was favored by suramin binding. A kinetic study of TNF dissociation by the same method produced values for the deoligomerization rate of trimer: on the average, koff approximately 4 x 10(-5) S-1 (t1/2 approximately 5 h) between 4 and 20 degrees C with little dependence on suramin concentration; at 37 degrees C, a sizable increase is observed in the presence of 1 mM suramin (koff = 2.3 x 10(-4) S-1, t1/2 = 0.8 h). Data of suramin inhibition on TNF receptor binding, as obtained after incubation times much shorter than the above half-life of trimer, indicate that suramin binding to TNF trimer is the early mechanism of receptor binding inhibition.
Assuntos
Suramina/farmacologia , Fator de Necrose Tumoral alfa/química , Humanos , Técnicas In Vitro , Cinética , Substâncias Macromoleculares , Conformação Proteica/efeitos dos fármacos , Receptores do Fator de Necrose Tumoral/metabolismo , Proteínas Recombinantes , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The association between low-density lipoprotein (LDL) and a series of well characterized dermatan and chondroitin sulfates has been investigated by means of the fluorescence anisotropy technique with competition experiments using a fluorescein-labeled high LDL-affinity heparin fraction as a reference. Preparations of glycosaminoglycan (GAG) with sulfation degrees varying over a wide range, as obtained by fractionation or by chemical modification, were chosen for this study. The influence of chain length, which had been found sizeable in a former study of heparin affinity for LDL, was taken into account with an empirical correction of dissociation constants. After this correction, a linear relationship was found between the logarithm of dissociation constants and the number of sulfate groups per disaccharide unit, ns, both for dermatan and chondroitin sulfates, and for heparins. At comparable ns values, however, dermatan sulfates and heparins, which contain L-iduronic acid in their backbone, show higher LDL-affinity than chondroitin sulfates, which contain only D-glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone.
Assuntos
Glicosaminoglicanos/metabolismo , Lipoproteínas LDL/metabolismo , Sítios de Ligação , Ligação Competitiva , Sequência de Carboidratos , Sulfatos de Condroitina/metabolismo , Dermatan Sulfato/metabolismo , Polarização de Fluorescência , Glicosaminoglicanos/química , Heparina/metabolismo , Humanos , Lipoproteínas LDL/química , Lipoproteínas LDL/isolamento & purificação , Matemática , Dados de Sequência Molecular , Peso MolecularRESUMO
Binding between low-density lipoproteins (LDL) and fluorescein-labeled heparin was studied quantitatively with a modified form of a published procedure [Cardin, A. D., Randall, C. I., Hirose, N., & Jackson, R. L. (1987) Biochemistry 26, 5513-5518], using fluorescence anisotropy titrations. Assumption of binding site equivalence satisfactorily interpreted experimental data. Accordingly, the apparent total capacity, n, and the average dissociation constant, Kd, were estimated as n approximately 24 disaccharides per LDL particle and Kd approximately 4 microM in 0.05 M HEPES/0.1 M NaCl, pH 7.4, 22 degrees C. Competition experiments with unlabeled heparins were exploited for the quantitative study of Kd as a function of heparin chain length and sulfation degree (ns = sulfate groups per disaccharide). The former parameter was investigated with a series of bovine lung heparin fractions with Mw ranging from 1,800 to 21,000 and constant sulfation degree (ns = 2.8 +/- 0.1). A series of physically fractionated or chemically modified heparins having 1.2 less than ns less than 3.5 were used to explore the dependence on sulfation degree. LDL affinity was found to increase with increasing both ns and Mw: an empirical Mw-1.6 dependence represented very well the chain length data set; a linear dependence was observed for log Kd as a function of ns, after appropriate allowance was made for chain length differences among samples. This regularity confirmed that LDL-heparin binding is mainly driven by electrostatic forces.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Heparina/metabolismo , Lipoproteínas LDL/metabolismo , Sulfatos/metabolismo , Apolipoproteína B-100 , Apolipoproteínas B/metabolismo , Sítios de Ligação , Ligação Competitiva , Fluoresceína , Fluoresceínas , Polarização de Fluorescência , Corantes Fluorescentes , Heparina/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The authors, in view of the continuously changing contagious diseases outline, deal with the problem of a better qualification and reorganization of the direct interventions in the contagious diseases prophylaxis. In this respect, the authors deem that the reporting of the cases must assume a primary importance and that all the locally operating health and social services, where the general medicine practitioners have an integrating part, ought to be redefined in their tasks and reorganized in view of the new outlines. So, it is necessary to found a more flexible reporting system. A bidirectional information flux model is also proposed between the public health-services and the general medicine practitioners.
Assuntos
Controle de Doenças Transmissíveis/métodos , Modelos Teóricos , Controle de Doenças Transmissíveis/legislação & jurisprudência , Doenças Transmissíveis/epidemiologia , Controle de Formulários e Registros/legislação & jurisprudência , Controle de Formulários e Registros/organização & administração , Serviços de Saúde/legislação & jurisprudência , Administração de Serviços de Saúde , Humanos , Itália/epidemiologiaRESUMO
Descriptive data on occupational accidents and diseases in the field of construction and particularly among builders are reported. They derive from publications of the National Insurance Institute for Occupational Accidents (INAIL) and refer to the Italian and Umbrian situation. Data show that the number and the severity of the accidents in this field are of great concern. The characteristics of the building work in our areas are too peculiar as the work is carried out in small building sites and lasts for a short period of time; subcontracting and piecework are widely diffused; health surveillance is nearly absent. One must take into account all of these characteristics when prevention programs are to be planned. Intervention priority must be given to a) information on occupational risks of contractors and workers; b) first level prevention; c) control and inspection activity. In this respect the A.A. report the results of the watch activity in 703 erecting yards by one to health unit's Department for the health security, safety and welfare of persons at work (period May 1985 - May 1988). The A.A. define a type of organization to achieve a continual intervention in the erecting yards.
Assuntos
Acidentes de Trabalho/prevenção & controle , Acidentes de Trabalho/mortalidade , Acidentes de Trabalho/estatística & dados numéricos , Humanos , Itália/epidemiologia , Risco , SegurançaRESUMO
The present report is a research on air samples taken in the operating theatres environment in the hospitals of Umbria to control in order the concentration of anaesthetics in use and to define ambient pollution and to propose changes. The A.A. have divided operating theatres in for groups to analyze the data: 1) operating theatres where there were both systems: air change system and air intake system; 2) operating theatres where there was only the air-change system; 3) operating theatres where there was only the air intake system; 4) operating theatres where there were no systems. These data have been compared with the limit values advised by N.I.O.S.H. The lowest value of pollution have been recorded in those operating theatres with both systems. The A.A. have also compared the ethrane or other alogenated anaesthetics values in the air-change system equipped operating theatres with those (values) found in the intake-air system equipped operating theatres. The lowest values have been recorded in those operating theatres with normal air-change system. Where changes have been made to improve the operating theatres environment, the A.A. have effectuated new controls and found lower values of the anaesthetics levels. The concentration of anaesthetics appeared lower then before.