RESUMO
Peer defending has been shown to protect bullied peers from further victimization and social-emotional problems. However, research examining defending behavior has demonstrated positive and negative social-emotional adjustment effects for defending students themselves. To explain these mixed findings, researchers have suggested that associations between defending behavior and social-emotional adjustment may be buffered by protective factors (i.e., defender protection hypothesis) or exacerbated by vulnerability or risk factors (i.e., defender vulnerability hypothesis). Consistent with these hypotheses, the present study aimed to investigate whether relationships with teachers and peers would moderate the association between defending behavior and social-emotional adjustment. This three-wave longitudinal study examined the association between peer nominated defending behavior and later self-reported depressive symptoms and self-esteem in 848 Belgian students in Grades 4-6 (53% girls; Mage = 10.61 years, SD = 0.90 at Wave 1). Peer nominated positive and negative teacher-student relationships (i.e., closeness and conflict) and peer relationships (i.e., acceptance and rejection) were included as moderators. Clustered multiple linear regression analyses demonstrated that defending behavior did not predict later depressive symptoms (ß = -0.04, p = .80) or self-esteem (ß = -0.19, p = .42). The lack of these associations could be explained by the defender protection and vulnerability hypotheses. However, contrary to our expectations, teacher-student closeness and peer acceptance did not play a protective role in the association between defending behavior and social-emotional adjustment (ß = -1.48-1.46, p = .24-0.96). In addition, teacher-student conflict and peer rejection did not put defending students at risk for social-emotional maladjustment (ß = -1.96-1.57, p = .54-0.97). Thus, relationships with teachers and peers did not moderate the association between defending behavior and later depressive symptoms and self-esteem.
Assuntos
Bullying , Depressão , Ajustamento Emocional , Relações Interpessoais , Grupo Associado , Instituições Acadêmicas , Autoimagem , Ajustamento Social , Estudantes , Humanos , Feminino , Masculino , Bullying/psicologia , Criança , Estudantes/psicologia , Estudos Longitudinais , Depressão/psicologia , Vítimas de Crime/psicologia , Bélgica , Professores Escolares/psicologiaRESUMO
Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies. We gave a total of 98 courses of cisplatin (escalated from 40 to 120 mg/m2) and melphalan (escalated from 12 to 30 mg/m2) to 30 patients with ip tumors, most of whom had residual ovarian cancer following iv cisplatin-containing regimens. Treatment was delivered in 2 L of 0.9% NaCl through a Tenckhoff catheter with or without a Port-a-Cath system every 28 days for one to nine cycles. Myelosuppression was dose-related and leukopenia was dose-limiting. The maximum tolerated dose was 120 mg of cisplatin/m2 and 20 mg of melphalan/m2. With the exception of treatment-induced nausea and vomiting, nonhematologic toxic effects were mild and no (or very little) local toxicity occurred. Pharmacokinetic analyses showed that the areas under the peritoneal concentration versus time curve averaged 16-fold and 17-fold more than the area under the plasma curve for cisplatin and melphalan, respectively. Objective responses were documented by third-look laparotomy in ovarian cancer patients with minimal (less than 2 cm) residual disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Melfalan/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/farmacocinética , Avaliação de Medicamentos , Feminino , Humanos , Injeções Intraperitoneais , Leucemia P388/tratamento farmacológico , Masculino , Melfalan/farmacocinética , Camundongos , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic. The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2. The maximum tolerated dose was 250 mg/m2. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks. There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2. Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement. Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients). Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days. Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed. Nausea and vomiting were uncommon and never severe. Alopecia and mucositis were rare. Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop. Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2. Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.
Assuntos
Antineoplásicos/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Medula Óssea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Feminino , Humanos , Infusões Parenterais , Cinética , Leucopenia/induzido quimicamente , Masculino , Menogaril , Pessoa de Meia-Idade , Nogalamicina/administração & dosagem , Nogalamicina/efeitos adversos , Nogalamicina/análogos & derivados , Nogalamicina/metabolismo , Risco , Pele/efeitos dos fármacos , Trombocitopenia/induzido quimicamente , Fatores de TempoRESUMO
PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bélgica/epidemiologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estatísticas não Paramétricas , Taxa de SobrevidaRESUMO
Minocycline hydrochloride hepatotoxic effect occurred in one patient. Unlike the usual histologic features of tetracycline-induced hepatic injury, fatty metamorphosis was predominantly macrovesicular . The patient recovered when drug therapy was withdrawn. Close observation of liver function variables is recommended in patients treated with high parenteral doses of minocycline, particularly in cases of pregnancy or renal disease.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Minociclina/efeitos adversos , Tetraciclinas/efeitos adversos , Doença Aguda , Feminino , Humanos , Fígado/patologia , Hepatopatias/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The French national programme for the neonatal screening of sickle cell disease (SCD) was set up in 1995. This screening is targeted at newborn infants at risk. Over 5 years, 115,480 newborn infants were tested from 80 maternity departments from the northern part of the Paris area. 250 Patients with SCD were identified--that is, one in 462 newborn infants tested. Carriers for a haemoglobin (Hb) variant are frequent (5.34%). Some uncommon Hb variants were also identified, which gave rise to pitfalls to the testing when associated with HbS: HbKorle-Bu, HbHope, HbBougardirey-Mali, and HbLadésirade (4% of SS-like profiles). OBJECTIVE: An effective screening strategy was developed to avoid these false positive and false negative responses. METHODS: Isoelectric focusing (IEF), the method of primary screening, is rapid and inexpensive. Cation exchange high performance liquid chromatography (CE-HPLC), which is automated, fast, and quantitative was selected as a secondary method. RESULTS: IEF diagnosed normal profiles in 89% of the tested samples from newborn infants. CE-HPLC identified most of the common Hb variants by their retention time and the measure of HbA/HbS ratio, important for the differential diagnosis between an asymptomatic HbS carrier and an HbS/beta+thal compound heterozygote. Furthermore, the high sensitivity of the CE-HPLC detected as little as 0.5% of a Hb variant. This avoided false negatives in samples from premature or transfused newborn infants. All samples with SS-like profiles were confirmed with a second CE-HPLC with another programme. A combination of these three methods confirmed the status of 99.7% of the samples from the tested newborn infants. Some cases required a reverse phase-HPLC method (for gamma-globin or alpha-globin chain variants). Finally, some exceptional samples required confirmation by testing DNA extracted with Güthrie paper for a precise diagnosis. CONCLUSIONS: This effective strategy combining several methods dramatically reduces the risk of errors. Many families are thus spared unnecessary worrying recalls. The only unavoidable cause of false positives remains the HbS/hereditary fetal Hb (HPFH).
Assuntos
Anemia Falciforme/diagnóstico , Triagem Neonatal/métodos , Anemia Falciforme/sangue , Anemia Falciforme/genética , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Erros de Diagnóstico , Triagem de Portadores Genéticos , Testes Genéticos/métodos , Variação Genética , Hemoglobina Falciforme/genética , Hemoglobina Falciforme/isolamento & purificação , Humanos , Recém-Nascido , Sondas de Oligonucleotídeos/genética , Paris , Sensibilidade e EspecificidadeRESUMO
Malignant lymphomas are occasionally encountered in the spine, where they are usually secondary deposits. The authors report the case of a primary non-Hodgkin lymphoma of the L1 vertebra in whom surgical treatment (two operations and double approach) was followed by radiotherapy and chemotherapy. The diagnosis is often made at a late stage, when neurological deficits produced by epidural compression become evident. The surgical treatment is only palliative but has several goals: obtaining a biopsy, improving the neurological symptoms through decompression, stabilizing and "rebuilding" the spinal column; it is performed using posterior, anterior or combined approaches which are discussed. The combined surgical, radiotherapeutic and polychemotherapeutic treatment is associated with a 5-year survival rate of 60-80%. Such a prognosis justifies the risk of surgery which will lead to a stable and lasting reconstruction.
Assuntos
Linfoma/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Humanos , Fixadores Internos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Ortopedia , Cuidados Paliativos , Neoplasias da Coluna Vertebral/patologia , Coluna Vertebral/patologia , Coluna Vertebral/cirurgiaRESUMO
Gene and genome duplications play a major role in the evolution of plant species. The Brassica nigra genome is highly replicated as a result of ancient polyploidization events. Two copies of the flowering time gene CONSTANS (COa and COb) have been identified in B. nigra, and previous studies showed that COa is functional. In the present study, the polymorphism of 92 COb alleles sampled in seven populations was analyzed. Both polymorphism and recombination levels were elevated and varied strongly among populations and 8% of COb alleles exhibit apparently disabling mutations. Sequence data, however, do not provide unambiguous support for the presence of relaxed selective constraint on COb as compared to known functional CO genes. On the one hand, some of the disabling mutations reached high-frequency arguing for a loss of function but, on the other hand, the ratio of nonsynonymous to synonymous nucleotide polymorphism and diversity is low and similar to that observed in other B. nigra CO and CO-like genes, supporting the conservation of some function. We also showed that COb is still transcribed. Finally, the flowering time of Arabidopsis thaliana co mutant plants transformed with COb alleles with and without apparent disabling mutations was similar. We propose that COb was retained for a long period after duplication, but a recent fixation of a detrimental mutation, possibly as an effect of a bottleneck, resulted in its nonfunctionalization. We also speculate as to the presence of subsequent selection for rapid degeneration of the gene.
Assuntos
Evolução Molecular , Topos Floridos/genética , Duplicação Gênica , Genes de Plantas , Mostardeira/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Mutação , Filogenia , Plantas Geneticamente Modificadas , Polimorfismo Genético , Pseudogenes , Fatores de Tempo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Some ants have an extraordinary form of social organization, called unicoloniality, whereby individuals mix freely among physically separated nests. This mode of social organization has been primarily studied in introduced and invasive ant species, so that the recognition ability and genetic structure of ants forming unicolonial populations in their native range remain poorly known. We investigated the pattern of aggression and the genetic structure of six unicolonial populations of the ant Formica paralugubris at four hierarchical levels: within nests, among nests within the same population, among nests of populations within the Alps or Jura Mountains and among nests of the two mountain ranges. Ants within populations showed no aggressive behaviour, but recognized nonnestmates as shown by longer antennation bouts. Overall, the level of aggression increased with geographic and genetic distance but was always considerably lower than between species. No distinct behavioural supercolony boundaries were found. Our study provides evidence that unicoloniality can be maintained in noninvasive ants despite significant genetic differentiation and the ability to discriminate between nestmates and nonnestmates.
Assuntos
Formigas/genética , Agressão/psicologia , Animais , Formigas/fisiologia , Comportamento AnimalRESUMO
Thirty one patients with solid tumors were entered into a phase I trial with idarubicin, a new anthracycline antibiotic with oral antitumor activity in animals. The drug was scheduled to be given for 4 consecutive weeks at doses ranging from 10 to 20 mg/m2. Leukopenia was the dose-limiting toxicity. Thrombocytopenia was occasionally seen. Since several patients could not receive the third and fourth administrations of the drug at 17.5 and 20 mg/m2, higher doses were administered only for 2 consecutive weeks. With this schedule, the maximum tolerated dose was 25 mg/m2 and leukopenia was again the dose-limiting toxicity. With both schedules, myelosuppression was highly variable and could not be related to prior therapy, bone or liver metastases, or performance status. Other toxicities were mild to moderate and were dominated by nausea and vomiting which were observed in 29% of the patients. Alopecia and mucositis were unfrequent and cardiac toxicity was not observed. Starting doses of 15 mg/m2 for 4 consecutive weeks or 20 mg/m2 for 2 consecutive weeks could be proposed for oral phase II studies with idarubicin, under careful pharmacokinetic monitoring.