RESUMO
Recently, rare mutations in the TARDBP gene have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to characterize the genetic variability of the TARDBP gene in a cohort of Sardinian ALS patients. The coding region of the gene was analyzed in 97 unrelated patients previously tested negative for superoxide dismutase (SOD1) mutations. The p.Ala382Thr (c.1144G>A) mutation was found in 30 patients (30.9%). The mutation was predominant in familial ALS patients (FALS) as it was represented in 24 of 30 FALS cases (80%) (p < 0.0003). Six cases were apparently sporadic (9% of sporadic ALS patients). No further mutation of TARDBP was found in our cohort of ALS patients. Patients carrying the mutation showed spinal site of onset in 24 cases (80%), an average age at onset of 54.7 ± 11.1 years, not significantly different from patients not harboring TARDBP mutations (56.7 ± 9.6) and a female:male gender ratio of 1:1.1. The haplotype analysis carried out using eight microsatellite markers flanking the gene showed a founder effect for this mutation. Finally, we estimated the age-specific penetrance of the TARDBP p.Ala382Thr mutation in an additional sample of 47 carriers (20 affected and 27 unaffected). The average penetrance to 70 years was 60% (95% confidence interval 41-79%). A trend toward a higher penetrance in males was observed. Even in the presence of a causal mutation, most of the ALS clinical heterogeneity, however, draws upon from a multifactorial context.
Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/genética , Taxa de Mutação , Mutação de Sentido Incorreto , Adulto , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Feminino , Efeito Fundador , Loci Gênicos , Haplótipos , Humanos , Itália/epidemiologia , Itália/etnologia , Masculino , Pessoa de Meia-Idade , Penetrância , Fatores SexuaisRESUMO
PURPOSE: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non-small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen. PATIENTS AND METHODS: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m(2)) and gemcitabine (1,000 mg/m(2)) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks. RESULTS: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m(2) in pretreated patients, whereas it continued to 150 mg/m(2) in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m(2) was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%. CONCLUSION: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Itália , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Vômito/induzido quimicamente , GencitabinaRESUMO
An active role of monoamine oxidase B (MAO-B) in the pathogenesis of neurodegenerative disorders such as Parkinson's disease has been proposed as the enzyme is known to be a generator of free radicals which seem to be responsible for neuron oxidative damage. We evaluated the influence of MAO-B in the pathogenesis of the sporadic forms of Amyotrophic lateral sclerosis (ALS) by studying the MAO-B allele distribution in 51 patients and 71 healthy controls. MAO-B did not directly result in a risk factor for ALS but seemed to strongly influence age at onset. The mean ALS onset age was significantly higher in individuals carrying allele 5 compared to individuals without this allele (60.4 +/- 8.1 vs. 52.1 +/- 10.3 years; P = 0.004). These results, in agreement with findings in the literature, suggest an increased MAO-B expression in ALS and support the hypothesis that neuronal cell death in neurodegenerative diseases is triggered by astroglial reaction.
Assuntos
Alelos , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Monoaminoxidase/genética , Adulto , Idade de Início , Idoso , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição por SexoRESUMO
OBJECTIVE: This phase III study was aimed at evaluating whether the addition of gemcitabine (G) to vinorelbine (V) could improve the survival and quality of life (QoL) of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, aged >or=70 years, were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1200 mg/m(2) plus V 30 mg/m(2) on days 1 and 8 every 3 weeks. Survival was the main end point of the study. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned on the first 60 patients per arm. RESULTS: In May 1999, an interim analysis was performed with the survival data of the first 120 eligible patients (V(arm)=60, G+V(arm)=60). Forty-nine patients had stage IIIB disease and 71 patients stage IV disease, median potential follow-up of 14 months (range; 3-22), 93 patients had died (G+V(arm)=41, V(arm)=52). Median survival time (MST) was 29 weeks and projected 1-year survival was 30% in the G+V(arm); these values were 18 weeks and 13% in the V(arm). At multivariate Cox analysis, the risk of death in the G+V(arm) compared with V(arm) was 0.48 (95% C1=0.29-0.79; P<0.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The ORR was 22 and 15% in the G+V and V(arms), respectively. Toxicity was not irrelevant in both arms. CONCLUSIONS: G+V treatment is associated with a significantly better survival than V alone in elderly NSCLC patients. The magnitude of the difference justifies the early closure of the study. The G+V regimen is now the SICOG reference regimen in this type of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/uso terapêutico , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Qualidade de Vida , Análise de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vinorelbina , GencitabinaRESUMO
Results obtained with a cyclophosphamide, methotrexate, vincristine, 5-FU and prednisone protocol in the treatment of advanced breast cancer are reported. The number of weekly courses proposed by Ansfield was varied. 53% remissions were noted. The effect of the variation introduced was assessed with reference to a much lower incidence of side-effects and a percentage of satisfactory results comparable with that of Ansfield. Nevertheless, it is felt that the treatment in question should be employed as a second choice when more efficacious protocols, such as those including adriamycin, cannot be used or have proved ineffective.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/radioterapia , Ciclofosfamida/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Vincristina/administração & dosagemRESUMO
2-alpha-methyl-17-beta hydroxy-androstan-3-one was given to advanced breast cancer patients whose general condition (preterminal in many cases) or haematological picture precluded other cytostatic management. Rapid progression of the tumour was noted in 65%, improvement in 15% and no change in 20%. It is felt that androgens alone should only be given where other more effective treatments are contraindicated. They can be associated with polychemotherapeutic courses to exploit their anabolising and antianaemic activity.
Assuntos
Androstanóis/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/cirurgia , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mastectomia , Menopausa , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
The results obtained with oestrogen treatment of diffuse malignant cancer of the breast are reported. Improvement was obtained in 50% of cases, 23.3% remained stationary and 26.6% worsened. Side effects were confined essentially to liver trouble of colostatic type, a disturbance that was temporary and closely linked with the drug dose employed. Some aspects of high dose antitumour hormone treatment are examined in detail: hormone dose in the induction phase and during maintenance, latency time before the appearance of the first signs of improvement, relationship between age, sexual endocrinal state and therapeutic result, correlation between time of onset of the disease, free interval and result obtained.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Etinilestradiol/uso terapêutico , Idoso , Doença Hepática Induzida por Substâncias e Drogas , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Fígado/efeitos dos fármacos , Pessoa de Meia-Idade , Metástase NeoplásicaAssuntos
Tecido Adiposo , Hipoglicemia/induzido quimicamente , Extratos de Tecidos , Adrenalectomia , Animais , Glicemia/análise , Encéfalo , Jejum , Injeções Intraperitoneais , Insulina/sangue , Fígado , Músculos , RatosAssuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/cirurgia , Neoplasias Retais/cirurgia , Vacina BCG/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/radioterapia , Fluoruracila/uso terapêutico , Humanos , Imunoterapia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Semustina/uso terapêuticoAssuntos
Diabetes Mellitus/sangue , Insulina/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Recursos Audiovisuais , Educação em Saúde Bucal , Adulto , Criança , Humanos , Televisão , Gravação de VideoteipeRESUMO
One hundred twenty freshly extracted human incisor teeth were bonded with several different brands of direct-bonding brackets and tested for retention prior to and after recycling of the brackets by two different commercially available methods. Measurements of shearing strengths were performed to observe any possible changes in the retentive properties of the brackets. The teeth were preconditioned by the application of adhesive material, followed by scaling and pumicing to remove any visible signs of composite. After bonding of the teeth and recording of retentive strengths, the brackets were recycled and the same teeth (after scaling and pumice) were rebonded and tested once more. A decrease in retentive strength was noted in all types of recycled brackets. One type of bracket showed a statistically significant change in strength, depending on the process used in recycling, while the other brackets did not show any difference between the two processes. A control consisting of twenty teeth bonded only once and twenty teeth bonded several times showed no statistically significant change in retention of brackets.
Assuntos
Aparelhos Ortodônticos , Fenômenos Químicos , Físico-Química , Resinas Compostas , Colagem Dentária/métodos , Estudos de Avaliação como Assunto , Humanos , Estresse MecânicoRESUMO
A conjugal case of amyotrophic lateral sclerosis (ALS) observed in Sardinia, Italy is reported. This is believed to be the ninth such observation described in the literature. The couple had lived together for 38 years in a house adjacent to the distillery they owned. No exogenous factors were revealed which could explain the genesis of the disease in either patients. Particularly, exposure to alcohol does not appear to have been involved in causing ALS. On the basis of statistical and epidemiological evaluations, the most likely explanation is that this association was purely coincidental.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Saúde da Família , Cônjuges , Feminino , Humanos , Itália/epidemiologia , Pessoa de Meia-IdadeRESUMO
The authors carried out an epidemiologic study on amyotrophic lateral sclerosis in Sardinia for the years 1957 through 1990. The duration of the disease and survival were significantly shorter in bulbar form. The distribution of ALS in various areas of the island was found to be not at all homogeneous. Mean yearly incidence showed no significant variations in the decades 1971-80 and 1981-90. In the last decade, an increase of bulbar forms was observed.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/mortalidade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Genética Populacional , Humanos , Incidência , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
Essential oils and their components are becoming increasingly popular as naturally occurring antimicrobial agents. In this work the chemical composition and the antimicrobial properties of Thymus essential oils and of their main components were determined. Three essential oils obtained from different species of Thymus growing wild in Sardinia and a commercial sample of Thymus capitatus oil were analysed. The essential oil components were identified by GC/MS analysis. The antimicrobial activity of the oils and components was determined against a panel of standard reference strains and multiple strains of food-derived spoilage and pathogenic bacteria, using a broth microdilution method. The GC/MS analysis showed that the major constituents of the oils were monoterpene hydrocarbons and phenolic monoterpenes, but the concentration of these compounds varied greatly among the oils examined. The results of the antimicrobial assay showed that essential oils extracted from Sardinian Thymus species have an antimicrobial activity comparable to the one observed in other thyme oils. It seems also confirmed that the antimicrobial properties of thyme essential oils are mainly related to their high phenolic content. Among the single compounds tested carvacrol and thymol turned out to be the most efficient against both reference strains and food-derived bacteria. The results of this study confirmed the possibility of using thyme essential oils or some of their components in food systems to prevent the growth of foodborne bacteria and extend the shelf-life of processed foods.
Assuntos
Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Lamiaceae/química , Monoterpenos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Antibacterianos/análise , Cromatografia Gasosa , Cimenos , Testes de Sensibilidade Microbiana , Terpenos/análise , Timol/análiseRESUMO
Twenty patients with disseminated breast cancer unresponsive to conventional chemotherapy and chemohormonotherapy were treated with an alternating sequential schedule of ethinyl estradiol and medroxyprogesterone on the basis of correlations between hormones and estrogen and progestin receptors. Of 19 evaluable patients, six underwent partial or complete remission, while five others showed minor responses.
PIP: A pilot study was conducted on 20 patients with disseminated breast cancer previously unresponsive to conventional chemotherapy and chemohormonotherapy. The 20 women were treated with ethinyl estradiol orally on days 1 and 2, medroxyprogesterone on days 3-9. After a 2-day interval, the sequential cycle was repeated. 10% of the women had complete remission and 20% more had partial remissions. More than 1/4 had minor remissions and 10% had their disease stabilized. Side effects with the therapy were practically absent. The rationale for the sequential therapy was suggested by interactions among hormones and receptors and the priming activity of estrogens on progesterone receptors. These preliminary results indicate that an alternated sequential therapy of ethinyl estradiol and medroxyprogesterone may be useful in managing advanced cancer.