RESUMO
OBJECTIVE: To systematically review the evidence on the effect of constraint-induced movement therapy compared with bimanual intensive training in children with unilateral cerebral palsy. DATA SOURCES: Seven electronic databases (Cinahl, Cochrane Library, EMBASE, Ovid MEDLINE, PEDro, PsycINFO, PubMed) were searched from database inception through December 2016. METHODS: A systematic review was performed using the American Academy of Cerebral Palsy and Developmental Medicine and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Standardised mean differences (effect sizes) were calculated for each study and outcome. RESULTS: Nine studies met the eligibility criteria. All studies provided level II evidence. Methodological quality was high in two studies, moderate in four studies and low in three studies. The methodology, participant and intervention characteristics were heterogeneous. The participants' ages ranged from 1.5 to 16 years. Their initial hand function ranged from Manual Ability Classification System Level I to Level III. The total intervention dose ranged from 24 to 210 hours and duration from one week to ten weeks. The studies measured outcomes assessing unimanual and bimanual hand and arm function, participation and attainment of individualised goals. Overall, the effect sizes did not favour one of the interventions at short- or long-term follow-up. The 95% confidence intervals were broad, indicating inaccurate precision of the effect sizes. Pooling of the data for a meta-analysis was judged to be of little clinical value owing to heterogeneity. CONCLUSION: It is not possible to conclude whether constraint-induced movement therapy or bimanual intensive training is more effective than the other in children with unilateral cerebral palsy.
Assuntos
Paralisia Cerebral/reabilitação , Modalidades de Fisioterapia , Restrição Física , HumanosRESUMO
BACKGROUND: During the last 15 years, high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has globally been performed for severe multiple sclerosis (MS). Most patients have been in progressive phase with long disease duration. As a rule, treatment effect has been minor or moderate. PATIENTS: Since 2004, we have performed HSCT in nine young patients with "malignant" relapsing-remitting MS. Criteria for treatment were short duration of disease; very frequent, severe relapses; recent improvement periods indicating potential for recovery after strong immunosuppression. FINDINGS: Median age at treatment was 27 (range 9-34) years, MS duration 26 (4-100) months, and annualized relapse rate 10 (4-12). Median Disability Status Scale (extended disability status scale, EDSS) at HSCT was 7.0 (3.5-8.0). Median follow-up time April 2008 is 29 (23-47) months. Median EDSS improvement is 3.5 (1.0-7.0), clearly surpassing most previous reports. One patient relapsed mildly with rapid recovery 7 months after HSCT. All patients are otherwise stable, median EDSS being 2.0 (0-6.0). Before HSCT, 61 relapses occurred in 82 patient months; during follow-up, one relapse in 289 patient months. CONCLUSION: This small series of patients with "malignant" relapsing-remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course. It further suggests that future criteria for HSCT in MS should be close to the present ones.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla Recidivante-Remitente/terapia , Índice de Gravidade de Doença , Doença Aguda , Adolescente , Adulto , Criança , Terapia Combinada , Avaliação da Deficiência , Feminino , Seguimentos , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Prevenção Secundária , Resultado do Tratamento , Adulto JovemAssuntos
Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/administração & dosagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Terapia Combinada , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Imunização Passiva , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Exame Neurológico/efeitos dos fármacos , Plasmaferese , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Recidiva , Resultado do TratamentoRESUMO
INTRODUCTION: Patients with multifocal motor neuropathy (MMN) usually respond to intravenous immunoglobulin (IVIG), but because of the short-lasting effect the treatment must be given repeatedly. Remission after treatment with high-dose cyclophosphamide has recently been reported in one patient refractory to IVIG. CASE REPORT: Here we report on a patient who responded to IVIG, but temporarily deteriorated dramatically after treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. Today the situation is the same as before the treatment with cyclophosphamide and blood stem cell transplantation, i.e. IVIG is given every 4 weeks. CONCLUSION: Our patient did not benefit from the treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. The effect of treatment with high-dose cyclophosphamide in MMN seems to be difficult to predict and that should be paid attention to if this type of treatment is considered.
Assuntos
Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Doença dos Neurônios Motores/terapia , Adulto , Terapia Combinada , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Doença dos Neurônios Motores/tratamento farmacológico , Transplante Autólogo , Falha de TratamentoRESUMO
In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels =9.5 microkat/l, bone marrow cellularity =70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Tioguanina/uso terapêutico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transformação Celular Neoplásica , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Tioguanina/efeitos adversosRESUMO
The assumption that soil neither acts as a source or a sink of chloride is evaluated by incubating soil cores in lysimeters in a climate chamber under controlled conditions. Some of the lysimeters acted as a sink while others acted as a source of chloride. Considerable amounts of organic chlorine were lost by leaching. The loss by leaching of organic chlorine could only explain part of the discrepancy in the lysimeters where the soil acted as a sink and it could certainly not explain the cases where the soil acted as a source. The storage of organic chlorine was four times larger than the storage of chloride and comparably small changes in the organic chlorine storage will thus have a considerable influence on the chloride budget. However, the soil was too heterogeneous to determine whether a change in the storage had taken place or not. It is concluded that the observed chloride surplus and also, at least to some extent, the observed chloride deficit, most likely was caused by net-changes in the storage of organic chlorine in soil. An inverse correlation was found between the initial chloride content of the soil and the imbalance in the chloride budget.Dry deposition of chloride is generally assumed to equal the run-off minus the wet deposition. Extrapolation to the field situation suggests that the output of organic chlorine by soil leachate is at risk to cause an underestimation of the dry deposition by about 25%.
Assuntos
Cloretos/análise , Hidrocarbonetos Clorados/análise , Poluentes do Solo/análise , Cloretos/química , Meio Ambiente , Monitoramento Ambiental/métodos , Hidrocarbonetos Clorados/química , Concentração de Íons de Hidrogênio , Modelos Químicos , Sensibilidade e Especificidade , Solo/análise , Solubilidade , Poluentes Químicos da Água/análiseRESUMO
Surface water and aqueous solutions of isolated organic matter from a humic rich lake in southern Sweden were exposed to artificial UV radiation to investigate the UV light induced influence on organic matter bound chlorine in natural systems. It was found that the photodegradation of organic matter bound chlorine was more pronounced than the photodegradation of organic carbon. After 120 h of irradiation of the isolated organic matter, only 35% of the initial organochlorine was still in the solution compared to about 70% of the dissolved organic carbon (DOC). A similar result was obtained for unfractionated surface water. Furthermore, our results indicate that the loss of organic chlorine was mainly due to a mineralization of organic chlorine into chloride ions. The total decrease of organic chlorine after 120 h was 32 microg Cl(org) l(-1), of which the major part disappeared in the initial irradiation phase. A similar increase was observed in the chloride concentration (34 microg Cl(-) l(-1)).
Assuntos
Água Doce/análise , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/efeitos da radiação , Raios Ultravioleta , Carbono/análise , Carbono/química , Fracionamento Químico/métodos , Cloretos/análise , Água Doce/química , Substâncias Húmicas/química , Hidrocarbonetos Clorados/análise , Suécia , Fatores de TempoRESUMO
It is still controversial how to treat elderly patients with acute myeloid leukaemia (AML), and results have been poor with most regimens. We report the long-term results of a randomised study performed by the Leukaemia Group of Middle Sweden during 1984-88 comparing two intensive chemotherapeutic drug combinations. Ninety patients >or=60-yr old with untreated AML were randomly allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and thioguanine (TAD) (43 patients) or a combination in which aclarubicin was substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%) entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in the TAA group (ns). The CR rate in patients
Assuntos
Aclarubicina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Tioguanina/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de TempoRESUMO
Chlorine is one of the most abundant elements on the surface of the earth. Until recently, it was widely believed that all chlorinated organic compounds were xenobiotic, that chlorine does not participate in biological processes and that it is present in the environment only as chloride. However, over the years, research has revealed that chlorine takes part in a complex biogeochemical cycle, that it is one of the major elements of soil organic matter and that the amount of naturally formed organic chlorine present in the environment can be counted in tons per km(2). Interestingly enough, some of the pieces of the chlorine puzzle have actually been known for decades, but the information has been scattered among a number of different disciplines with little or no exchange of information. The lack of communication appears to be due to the fact that the points of departure in the various fields have not corresponded; a number of paradoxes are actually revealed when the known pieces of the chlorine puzzle are fit together. It appears as if a number of generally agreed statements or tacit understandings have guided perceptions, and that these have obstructed the understanding of the chlorine-cycle as a whole. The present review enlightens four paradoxes that spring up when some persistent tacit understandings are viewed in the light of recent work as well as earlier findings in other areas. The paradoxes illuminated in this paper are that it is generally agreed that: (1) chlorinated organic compounds are xenobiotic even though more than 1,000 naturally produced chlorinated compounds have been identified; (2) only a few, rather specialised, organisms are able to convert chloride to organic chlorine even though it appears as if the ability among organisms to transform chloride to organic chlorine is more the rule than the exception; (3) all chlorinated organic compounds are persistent and toxic even though the vast majority of naturally produced organic chlorine is neither persistent nor toxic; (4) chlorine is mainly found in its ionic form in the environment even though organic chlorine is as abundant or even more abundant than chloride in soil. Furthermore, the contours of the terrestrial chlorine cycle are outlined and put in a concrete form by constructing a rough chlorine budget over a small forested catchment. Finally, possible ecological roles of the turnover of chlorine are discussed.
Assuntos
Cloro , Cloretos/metabolismo , Cloro/química , Cloro/metabolismo , Cloro/toxicidade , Compostos Clorados/química , Modelos Químicos , Modelos Moleculares , Periodicidade , Xenobióticos/químicaRESUMO
The aims of the present study were (1) to investigate and quantify the pharmacokinetics, including inter-occasion variability and covariate relationships, of busulphan in BMT patients and (2) to develop a user-friendly initial dosing and therapeutic drug monitoring (TDM) strategy for the treatment of those patients with busulphan. The pharmacokinetics of busulphan was studied in 64 adults and 12 children who received busulphan (1 mg/kg) four times daily for 4 days. A one-compartment model with first order absorption and a lag time was sufficient in describing the concentration-time profile. Oral clearance (CL/F) was found to be correlated to weight (+1.2%/kg), ALT (-13%/microcat/l) and concomitant phenytoin treatment (+21%). CL/F and the volume of distribution (V/F) were estimated to 9.23 l/h and 39.3 l, respectively, in a typical individual. Inter-occasion variability (9.4%) in CL/F was estimated to be less than inter-individual variability (28%), a prerequisite for the value of TDM. Bayesian CL/F estimates based on three samples were in good accordance with those based on all samples. The final population model was implemented into the program Excel. The resulting flexible and easy to use dosing program might be used for both initial and, requiring only three plasma samples, maintenance dose individualization of busulphan therapy.
Assuntos
Antineoplásicos Alquilantes/farmacocinética , Transplante de Medula Óssea , Bussulfano/farmacocinética , Simulação por Computador , Modelos Biológicos , Condicionamento Pré-Transplante/métodos , Administração Oral , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/sangue , Área Sob a Curva , Teorema de Bayes , Compartimentos de Líquidos Corporais , Peso Corporal , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/sangue , Criança , Pré-Escolar , Clonazepam/administração & dosagem , Clonazepam/farmacocinética , Clonazepam/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Interações Medicamentosas , Feminino , Variação Genética , Humanos , Lactente , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fenitoína/administração & dosagem , Fenitoína/farmacocinética , Fenitoína/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Interface Usuário-Computador , Irradiação Corporal TotalRESUMO
The aim of the present study is to investigate whether exo-enzymatically mediated chlorination of fulvic acid (FA) results in the formation of chlorinated groups within the macromolecules which correspond to those which were previously detected in soil and surface water samples. The chlorination was carried out by exposing FA to a commercial chloroperoxidase (CPO) in the presence of chloride and hydrogen peroxide. The exposed FA was then chemically degraded using an oxidative technique and finally analysed for four different aromatic groups and their chlorinated analogues. The particular aromatic groups included were the methyl esters of 4-ethoxybenzoic acid, 3-methoxy-4-ethoxybenzoic acid, 3,4-diethoxybenzoic acid, and 3,5-dimethoxy-4-ethoxybenzoic acid, along with their mono- and dichlorinated analogues. Prior to the chemical degradation procedure, the FA was analysed for AOX (adsorbable organic halogens) and chlorinated acetic acids. The original FA contained 1.4 mg Cl(org) g(-1) and detectable amounts of two chlorinated aromatic groups. After exposure to the enzyme, the concentration of AOX increased to 44.3 mg Cl(org) g(-1) and detectable amounts of four chlorinated aromatic groups as well as di- and trichloroacetic acid were found.
Assuntos
Benzopiranos/química , Benzopiranos/metabolismo , Cloreto Peroxidase/metabolismo , Acetatos/química , Cloreto Peroxidase/química , Compostos Clorados/química , Peróxido de Hidrogênio/químicaRESUMO
Busulphan and cyclophosphamide (Bu/CP) are widely used in preparative regimens for bone marrow transplantation. Many studies have shown a wide variation in busulphan pharmacokinetics. Moreover, higher rates of liver toxicity were reported in Bu/CP protocols than in a total body irradiation (TBI)-containing regimen. In the present paper we investigated the effect of the time interval between the last dose of busulphan and the first dose of cyclophosphamide on the pharmacokinetics of CP and its cytotoxic metabolite 4-hydroperoxycyclophosphamide (4-OHCP). Thirty-six patients undergoing bone marrow transplantation (BMT) were included in the study. We also investigated the occurrence of veno-occlusive disease, mucositis and graft-versus-host disease. Ten patients conditioned with CP followed by TBI served as a control group (TBI). Twenty-six patients were conditioned with Bu/CP. The patients received Bu (1 mg/kg x 4 for 4 days), followed by CP (60 mg/kg for 2 days) administered as a 1-h infusion. Patients received their CP therapy either 7-15 h (group A, n = 12) or 24-50 h (group B, n = 14) after the last dose of Bu. None of the patients were given phenytoin or any other drug known to enhance CP metabolism. The administration of CP less than 24 h after the last dose of Bu resulted in: (1) a significantly (P = 0.003) lower clearance for cyclophosphamide was observed in group A (0.036 l/h/kg) compared to 0.055 and 0.055 l/h/kg, in the B and TBI groups, respectively; (2) significantly (P = 0.002) longer elimination half-life in group A (10.93 h) than in groups B and TBI (6.87 and 7.52 h, respectively); (3) significantly (P < 0.001) lower exposure to the cytotoxic metabolite (4-OHCP), expressed as the ratio AUC4-OHCP/AUCCP, in group A (0.0053) than that obtained in group B (0.013) and group TBI (0.012); (4) the patients in group A had a significantly (P < 0.05) higher incidence of VOD (seven of 12) than the other groups, B and TBI (2/14 and 1/10, respectively); and (5) mucositis was significantly higher in group A patients (8/12), being seen in only one patient in group B and none in the TBI group. The present study has shown that the interval between busulphan and cyclophosphamide administration can negatively affect the pharmacokinetics of cyclophosphamide and its cytotoxic metabolite. We conclude that the timing of CP administration must be considered in order to improve drug efficacy and reduce conditioning-related toxicity.
Assuntos
Transplante de Medula Óssea , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Adolescente , Adulto , Bussulfano/efeitos adversos , Criança , Ciclofosfamida/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Autólogo , Transplante HomólogoAssuntos
Anfotericina B/efeitos adversos , Fosfatidilcolinas/efeitos adversos , Fosfatidilgliceróis/efeitos adversos , Adolescente , Adulto , Idoso , Anfotericina B/toxicidade , Antifúngicos/efeitos adversos , Antifúngicos/toxicidade , Bilirrubina/sangue , Transplante de Medula Óssea , Creatinina/sangue , Combinação de Medicamentos , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/etnologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/toxicidade , Fosfatidilgliceróis/toxicidade , Países Escandinavos e Nórdicos/epidemiologiaRESUMO
This study was performed to analyse differences in T-cell proliferation induced by a latent virus, varicellae-zoster virus (VZV) and a non-latent virus, measles virus, in patients after allogeneic bone marrow transplantation (BMT). The lymphoproliferative response to measles antigen, VZV-antigen (VZV-ag), and phytohemagglutinin (PHA) was measured by 3H-thymidine incorporation, and interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) analyses in supernatants after in vitro stimulation of peripheral blood mononuclear cells (PBMC) from 22 patients and 18 healthy controls. The cytokine levels were correlated with T-cell subsets by FACS analyses. At the antigen concentrations used, VZV-ag induced higher levels of IFN-gamma (p < 0.05) than did the measles antigen, whereas the levels of IL-10 were similar. Patients without a cell mediated immune (CMI) response to VZV-ag or measles antigen had lower CD4+ T-cell counts than did controls (p < 0.01 in both cases) and lower IFN-gamma production after non-specific PHA stimulation (p <0.01). The IFN-gamma and IL-10 levels after measles antigen stimulation correlated with the number of CD4+ T-cells (p < 0.01 and p < 0.05, respectively), and after VZV-ag mainly to the number of CD8+ T-cells (p < 0.01 and p < 0.05, respectively). These results suggest that there is a difference in the types of T-cells that respond to VZV-ag and measles antigen stimulation, respectively. The impaired CMI response to viral antigens seen in many patients may be explained both by a low number of CD4+ T-cells and by a cell dysfunction.
Assuntos
Transplante de Medula Óssea/imunologia , Herpesvirus Humano 3/imunologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Leucócitos Mononucleares/virologia , Vírus do Sarampo/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Antígenos Virais/imunologia , Células Cultivadas , Criança , Pré-Escolar , Seguimentos , Humanos , Imunidade Celular/imunologia , Lactente , Ativação Linfocitária , Pessoa de Meia-Idade , Fito-Hemaglutininas/imunologiaRESUMO
The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.
Assuntos
Formação de Anticorpos/imunologia , Leucemia/imunologia , Linfoma/imunologia , Toxoide Tetânico/imunologia , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The aims of this study were to assess long-term immunity and reimmunization responses against tetanus toxoid in recipients of autologous stem cell grafts and to compare immune status in patients who underwent ABMT or autologous blood stem cell transplantation (APBSCT). Ninety patients were included in the study; 52 had received ABMT and 38 APBSCT. Thirty of 52 ABMT patients (58%) and 25 of 38 APBSCT patients (66%) had protective antibody levels against tetanus before transplantation (P = NS). The rate of seropositivity had decreased at 1 year after transplantation; 15 of 52 (29%) ABMT patients and 18 of 38 (47%) APBSCT patients (P = NS) were still positive after 1 year. There were no cases of spontaneous recovery in seronegative patients. Most patients were reimmunized with three doses of tetanus toxoid given at 12, 13, 14 and or 18 months after transplantation. All immunized patients had protective immunity against tetanus at 1 year after vaccination. These results suggest that humoral immunity is defective both after ABMT and after APBSCT and in both cases the loss of immunity seems to be similar. Reimmunization of patients who have undergone ABMT or APBSCT is necessary to obtain protective immunity against tetanus.
Assuntos
Transplante de Medula Óssea/imunologia , Transplante de Células-Tronco Hematopoéticas , Toxoide Tetânico/imunologia , Tétano/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Transplante AutólogoRESUMO
Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.
Assuntos
Anemia/tratamento farmacológico , Anemia/fisiopatologia , Eritropoetina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Síndromes Mielodisplásicas/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Sixty-four consecutive cases of allogeneic (n = 16), autologous (n = 47) or syngeneic (n = 1) bone marrow transplantation (BMT) in children with haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed to assess the incidence, clinical presentation and outcome of liver disease. Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the pre-transplant check-up. During the first 100 d post-transplant, 81% of the patients had impaired liver function as documented by various biochemical parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute graft vs host disease (GVHD) with liver involvement (grades II-III). No patient died of liver disease. During the late post-transplant follow-up, one patient developed HCV hepatitis after packed erythrocyte transfusion. Four patients were diagnosed as having chronic GVHD with liver involvement; three of them also had an episode of CMV hepatitis. At their latest follow-up, the patients with chronic GVHD had aminotransferase values 1.5-3 times the normal, whereas all other long-term survivors had normal or near-normal liver function tests. We conclude that the incidence of serious liver disease was low in this paediatric population of bone marrow recipients.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Hepatopatias/etiologia , Adolescente , Criança , Pré-Escolar , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Hepatite C/etiologia , Hepatite Viral Humana/etiologia , Humanos , Incidência , Lactente , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Masculino , PrognósticoRESUMO
In this paper we report about the Danish Year of the Brain 1997 because it may serve as a model for other countries. It was possible in Denmark to organize a very large scale effort which has been well received by the general public and which has significantly improved the image of the neurological disciplines. The resources spent on nationwide initiatives in the Danish Year of the Brain are more than 2 million ECU in a country with 5 million inhabitants. In addition, however, considerable amounts were spent in each county of Denmark. Since all professionals have worked for free, innumerable hours of work have not been budgeted. In fact, the Danish Year of the Brain has been the largest privately organized health campaign ever held in Denmark and it has been so successful that the Danish Heart Association, which is old, well organized and extremely strong financially, has been worried about the shift of attention from the heart to the brain. Copyright 1998 Lippincott Williams & Wilkins
RESUMO
BACKGROUND: With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first-line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60-80%. However, only 10-20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation. METHODS: We report here our initial experiences of the use of high-dose chemotherapy supported by ASCT for patients with high-risk ovarian cancer. Two patients were treated at Uppsala University Hospital in 1992 and four patients at Turku University Central Hospital in 1994. RESULTS: The first four patients treated either after heavy previous chemotherapy or recurrent disease relapsed within 5-10 months. Two patients received high-dose therapy as part of first-line treatment. One of them had a relapse 18 months after therapy, the other one has been disease free for 28 months. No toxic deaths occurred, but the patients had neutropenic febrile episodes and moderate to severe gastrointestinal toxicity. CONCLUSIONS: Coordinated efforts in Nordic countries are indicated to evaluate the usefulness of high-dose therapy supported by ASCT in the treatment of advanced ovarian cancer.