RESUMEN
Sugarcane bagasse is an abundant and renewable agricultural waste material generated by the sugar industry worldwide. The use of sugarcane bagasse as a bio-coagulant precursor in water treatment is an eco-friendly and cost-effective approach that has shown great potential. This article reviewed the prospects and challenges of utilizing sugarcane bagasse as a bio-coagulant precursor for water treatment. The article reviewed past studies and explored the properties and chemical composition of sugarcane bagasse and the bioactive compounds that can be extracted from it, as well as their potential coagulation performance in water treatment. It was observed that there are few studies that have been published on the subject. The effectiveness of sugarcane bagasse-based coagulants varies depending on several factors, such as pH, temperature, and water quality parameters. However, the lack of standardization in the production of sugarcane bagasse-based coagulants is a challenge that needs to be addressed. Additionally, the optimization of extraction and processing methods to enhance the effectiveness of sugarcane bagasse-based coagulants needs to be investigated further. In conclusion, the use of sugarcane bagasse as a bio-coagulant precursor holds great promise for the future of sustainable water treatment. The potential for sugarcane bagasse to be used as a bio-coagulant precursor highlights the importance of exploring alternative and sustainable materials for water treatment.
RESUMEN
Phytoplankton and epipelon assemblages form the main constituents, and they are producers in aquatic ecosystems, such as streams and rivers. This study was carried out between May 2008 and April 2009 to determine the impacts of polluted water on species variations, compositions, and community metrics in phytoplankton and epipelon at six stations on Ankara Stream. A total of 231 taxa were recorded during the study period, with 131 Bacillariophyta, 3 Charophyta, 41 Chlorophyta, 30 Cyanobacteria, 25 Euglenophyta, and 1 Ochrophyta. Heterogeneity of the stream stations was determined by the use of hierarchical cluster analysis (HCA). Community metrics were compared by using non-parametric tests, while canonical correspondence analysis (CCA) was used for the relationships between environmental variables and species. Variations in water quality and species composition along the stream flow revealed a significant spatial heterogeneity (p < 0.05). However, the upper stations of the stream were represented by unpolluted water quality with low nutrients and conductivity, and the mid- and downstream stations were characterized by high concentrations of ammonia (up to 60 mg L-1) and o-phosphate (up to 25 mg/L), with low concentrations of dissolved oxygen (< 1 mg L-1). The results, clearly supported by indicator taxa, showed that various domestic and industrial discharges affected the increase in pollution and the spatial heterogeneity. The findings obtained in this study will contribute to future improvements in Ankara Stream watershed studies.
Asunto(s)
Diatomeas/metabolismo , Monitoreo del Ambiente/métodos , Residuos Industriales/análisis , Fitoplancton/metabolismo , Plantas/metabolismo , Ríos/química , Contaminación del Agua/efectos adversos , Contaminación del Agua/análisis , Amoníaco/análisis , Biodiversidad , Cianobacterias/clasificación , Cianobacterias/metabolismo , Ecosistema , Euglénidos/metabolismo , Oxígeno/análisis , Fosfatos/análisis , Plantas/clasificación , Turquía , Calidad del AguaRESUMEN
Members of the histone deacetylase (HDAC) family exhibit great promise as potential drug targets in pediatric tumors including neuroblastoma, medulloblastoma, ependymoma and Ewing's sarcoma. HDAC inhibitors of various structural classes have shown anti-tumoral effects in pre-clinical pediatric tumor models as single agents or in combination treatments. Suberoylanilidehydroxamic acid (SAHA=vorinostat) is the most clinical advanced compound of the class and was approved by the US FDA in October 2006 for the treatment of refractory cutaneous T-cell lymphoma. In this phase I/II trial, pediatric patients with relapsed solid tumors, lymphoma or leukemias are treated according to an individualized dose escalation concept ensuring each individual patient to receive his optimal dose with respect to toxicity and efficacy. The study is accompanied by an extensive pharmacokinetic, pharmacodynamic and biomarker program.
Asunto(s)
Antineoplásicos/administración & dosificación , Inhibidores de Histona Desacetilasas/administración & dosificación , Ácidos Hidroxámicos/administración & dosificación , Leucemia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Administración Oral , Adolescente , Antineoplásicos/farmacocinética , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Inhibidores de Histona Desacetilasas/farmacocinética , Humanos , Ácidos Hidroxámicos/farmacocinética , Leucemia/sangre , Cuidados a Largo Plazo , Linfoma/sangre , Masculino , Recurrencia Local de Neoplasia/sangre , Neoplasias/sangre , VorinostatRESUMEN
BACKGROUND AND PURPOSE: The biosorption of Cr(VI) from aqueous solution has been studied using free and immobilized Pediastrum boryanum cells in a batch system. The algal cells were immobilized in alginate and alginate-gelatin beads via entrapment, and their algal cell free counterparts were used as control systems during biosorption studies of Cr(VI). METHODS: The changes in the functional groups of the biosorbents formulations were confirmed by Fourier transform infrared spectra. The effect of pH, equilibrium time, initial concentration of metal ions, and temperature on the biosorption of Cr(VI) ion was investigated. RESULTS: The maximum Cr(VI) biosorption capacities were found to be 17.3, 6.73, 14.0, 23.8, and 29.6 mg/g for the free algal cells, and alginate, alginate-gelatin, alginate-cells, and alginate-gelatin-cells at pH 2.0, which are corresponding to an initial Cr(VI) concentration of 400 mg/L. The biosorption of Cr(VI) on all the tested biosorbents (P. boryanum cells, alginate, alginate-gelatin, and alginate-cells, alginate-gelatin-cells) followed Langmuir adsorption isotherm model. CONCLUSION: The thermodynamic studies indicated that the biosorption process was spontaneous and endothermic in nature under studied conditions. For all the tested biosorbents, biosorption kinetic was best described by the pseudo-second-order model.
Asunto(s)
Cromo/metabolismo , Microalgas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Adsorción , Alginatos/química , Biodegradación Ambiental , Cromo/química , Gelatina/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Cinética , Metales Pesados/química , Metales Pesados/metabolismo , Microalgas/ultraestructura , Propiedades de Superficie , Termodinámica , Contaminantes Químicos del Agua/química , Purificación del AguaRESUMEN
The evaluation of diagnostic tests (DT) or procedures is not subject to uniform regulations. However, a thorough evaluation of DT which are intended for use in routine medical practice is advisable or even indispensible for economic, medical, and ethical reasons. This article addresses some important aspects of this evaluation: the facets of "evaluating a DT", common validity measures for qualitative and quantitative DT, the applicability and generalizability of estimates of diagnostic accuracy, objectives and design of studies for evaluating DT, as well as specific methodological problems of theses studies.
Asunto(s)
Ensayos Clínicos como Asunto/legislación & jurisprudencia , Pruebas Diagnósticas de Rutina/métodos , Biomarcadores de Tumor/sangre , Ensayos Clínicos como Asunto/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Alemania , Humanos , Tamizaje Masivo/legislación & jurisprudencia , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Neoplasias/sangre , Neoplasias/diagnóstico , Valor Predictivo de las Pruebas , Curva ROC , Proyectos de Investigación/legislación & jurisprudencia , Proyectos de Investigación/estadística & datos numéricosRESUMEN
We investigated whether there is a relationship between loss of p16(INK4a) protein expression and p53 alterations in head and neck squamous cell carcinomas (HNSCCs). For this purpose, immunohistochemistry was performed on tissue microarrays of 664 tumours; this represents the largest HNSCC cohort studied for molecular biomarkers. Loss of p16(INK4a) protein expression was associated with aberrant p53 expression (negative or overexpressed) in the total cohort, and with TP53 mutations in 200 tumours analysed (p < 0.0001 each). Both loss of p16(INK4a) expression and p53 alterations differed significantly across both tumour sites and stages, being more prevalent in the hypopharynx than in the other tumour sites and in advanced tumour stages. As a possible link between p53 status and p16(INK4a) loss, we found that increased DNA methyltransferase 1 protein levels occurred preferentially in tumours with aberrant p53 (p = 0.001) and negative p16(INK4a) expression (p = 0.0004). In the total cohort, there was a borderline significant difference in patient survival across three p16(INK4a) expression levels (negative, positive, high), with loss of p16(INK4a) expression showing shortest survival. It is suggested that loss of p16(INK4a) expression and p53 alterations should be viewed as related events involved in the early carcinogenic process.
Asunto(s)
Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes p16 , Genes p53 , Neoplasias de Cabeza y Cuello/genética , Análisis por Micromatrices , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/genética , Eliminación de Gen , Expresión Génica , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/mortalidad , Inmunohistoquímica/métodos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/mortalidad , Neoplasias de la Boca/genética , Neoplasias de la Boca/mortalidad , Mutación , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/mortalidad , Tasa de SupervivenciaRESUMEN
Postoperative surveillance is an important part of the curative therapy of colorectal cancer patients. The effort and effectiveness of these surveillance programs are controversially discussed. We analyzed the practiced follow-up of patients who had undergone a curative resection of colorectal cancer to demonstrate the difficulty to validate the performed surveillance program and to point out possible improvements. For a follow-up period of 37 months (median) we included 530 patients with at least one postoperative examination. 70 patients ended the follow-up prematurely - out of these 56 % quit the surveillance during the first 18 months. Another 68 patients died during the follow-up period. Cancer recurred in 28 % of the patients (n = 109 metastasis, n = 26 local recurrences, 18 patients developed a secondary cancer). 90 % of these recurrences occurred within the first three years. 3525 follow-up examinations took place within 79 months. Patient histories and physical examinations were not helpful for the diagnosis of local recurrences; neither were laboratory routine screenings meaningful. Carcinoembryonic antigen (CEA) and CA 19 - 9 tests, ultrasonographic studies, chest XD-rays and colonoscopic procedures had a higher diagnostic value on the other hand. We demonstrated the problematic nature of the evaluation of different follow-up tests concerning their validity as they were part of a complex postoperative surveillance program. It is also important to point out that the success of the postoperative surveillance depends strongly on the compliance of the patients. To increase this compliance we suggest that the follow-up of patients should be more strongly oriented towards the incidence of recurrences.
Asunto(s)
Cuidados Posteriores/estadística & datos numéricos , Neoplasias Colorrectales/cirugía , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Cooperación del Paciente/estadística & datos numéricos , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Colonoscopía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Diagnóstico por Imagen , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/diagnóstico , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Valor Predictivo de las Pruebas , Tasa de SupervivenciaRESUMEN
BACKGROUND: Prospective randomized studies on mistletoe therapy repeatedly demonstrated that there is a basic problem in the matter of enrolling the appropriate number of patients within a reasonable amount of time. Most studies have to face this problem. However, recent experience suggests that this problem is more pronounced in the case of mistletoe treatment of cancer patients. OBJECTIVE: Possibility of recruitment and randomization of breast cancer patients for a mistletoe study. PATIENTS: During a period of 28 months every patient was registered who was admitted to the Gynecological Hospital of the University of Heidelberg because of suspected cancer. RESULTS: Out of 1,922 patients who were operated on for breast tumor, 521 first met the inclusion and exclusion criteria. 154 out of these 521 patients agreed to take part in the study. After availability of the final results on tumor staging and the therapy plan for conventional treatment, 80 out of the 154 women had to be excluded from the study. From the remaining 74 patients (48%), however, only 29 (39%) would have agreed to take part in a randomized mistletoe study. CONCLUSIONS: This confirms our suspicion that the difficulties of enrollment and randomization in the case of mistletoe studies exceed those of studies conducted in conventional oncology. The reasons for this dramatic effect and the possibility of alternative study designs are discussed.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Muérdago , Fitoterapia , Extractos Vegetales/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Femenino , Humanos , Preparaciones de Plantas/uso terapéutico , Proteínas de Plantas/uso terapéutico , Estudios Prospectivos , Proteínas Inactivadoras de Ribosomas Tipo 2 , Factores de Tiempo , Toxinas Biológicas/uso terapéuticoRESUMEN
BACKGROUND: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity. PATIENTS AND METHODS: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for therapy according to the International Society of Pediatric Oncology Trial and Study 9. Therapy for relapse depended on site of relapse and therapy already received. Follow-up included inquiries for morbidity. Prognostic factors for relapse and death were evaluated. RESULTS: Five-year survival of WTs was 89.5%; 98.2% (385 of 392) of survivors had a follow-up of 5 years (range 0.8-12.6; median 8). In non-anaplastic WTs, young age (<2 years) was of significance (P = 0.026) for a better survival. Non-anaplastic WTs (407 patients) had a 5-year survival of 92.3%, versus 48.5% in anaplastic WTs (33 patients), and a 5-year relapse-free survival of 87.6% versus 42.4%. Survival after relapse was significantly worse for anaplastic than for non-anaplastic WTs (residual 3-year survival 11.8% versus 54.3%; P <0.0001). In preoperatively treated WTs, anaplasia was a strong prognostic factor for death [relative risk (RR) 4.7], followed by poor response to preoperative therapy (RR 3.6), stage IV (RR 3.2) and abdominal stage III (RR 2.2). Low abdominal stages (Asunto(s)
Neoplasias Renales/terapia
, Recurrencia Local de Neoplasia
, Tumor de Wilms/terapia
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Niño
, Preescolar
, Supervivencia sin Enfermedad
, Femenino
, Estudios de Seguimiento
, Humanos
, Neoplasias Renales/patología
, Masculino
, Morbilidad
, Estadificación de Neoplasias
, Pronóstico
, Factores de Riesgo
, Tumor de Wilms/patología
Asunto(s)
Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Humanos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy according the International Society of Paediatric Oncology trial & study 9. Standardised preoperative therapy with dactinomycin and vincristine for 4-8 weeks was generally applied in patients between 0.5 and 16 years with localized renal tumors and imaging typical for WT. In 99.5% of cases representative material was sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified Beckwith & Palmer criteria were used. Reduction in volume measured by imaging prior to chemotherapy and surgery was used to assess response (poor response: reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of patients treated with immediate surgery and 12.4% of patients with preoperative therapy in the age group up to 12 months. The difference in age (P = 0.022) was linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58 and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed: stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of epithelial WT) but none relapsed. In the other WT with viable tumor left after preoperative therapy > 70% had good response, poor response was a risk factor (P = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be used in WT after preoperative therapy to stratify postoperative therapy in future. A milder therapy could be tested in differentiated WT at low stages and an intensified in the others with viable tumor left and poor response, i.e., mainly blastemal WT.
Asunto(s)
Neoplasias Renales/patología , Tumor de Wilms/patología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Dactinomicina/administración & dosificación , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Renales/clasificación , Neoplasias Renales/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Tumor de Wilms/clasificación , Tumor de Wilms/tratamiento farmacológicoRESUMEN
The thickness of the stratum corneum was measured by optical coherence tomography at the center and sides of the tactile elevations of all fingers in 87 healthy volunteers and 18 people with diabetes who performed regular glucose self-control. The cornified epidermis was thickest at the thumbs, and thickness decreased toward the little finger. The cornified epidermis was thinner at the sides of the tactile elevations than at the center, and it was thinner in women than in men. In people with diabetes, the cornified epidermis of the fingers most frequently used for capillary blood sampling was not conspicuously thickened.
Asunto(s)
Epidermis/anatomía & histología , Dedos/anatomía & histología , Adolescente , Adulto , Diabetes Mellitus/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
PURPOSE: Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find out if there is a substantial difference in outcome between these approaches, we performed a randomized prospective study. METHODS AND MATERIALS: Between 1994 and 1998, 152 eligible patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31) were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and mediastinum. RESULTS: One-year survival rate for all patients was 37% with no significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76). As far as can be judged from limited data available, palliation was adequate and similar for the two treatment arms. Apart from expected differences in the time course of esophagitis, acute side effects were moderate and equally distributed. No severe late effects were observed. CONCLUSIONS: In the present randomized trial, survival and available data on palliation were not different after cf to 60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are not suitable for radical treatment approaches, the prescription of a palliative short-term irradiation appears preferable compared to cf over several weeks.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Fraccionamiento de la Dosis de Radiación , Esofagitis/etiología , Femenino , Humanos , Estado de Ejecución de Karnofsky , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Paliativos , Estudios Prospectivos , Neumonitis por Radiación/etiología , Análisis de Regresión , Tasa de Supervivencia , Factores de TiempoRESUMEN
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagnostic validation studies (Phase I to IV). The diagnostic value of a test can be described by indexes like sensitivity, specificity and predictive values. Sensitivity and specificity are so-called nosological probabilities whereas predictive values describe the probabilities of the disease given a positive or negative test result, respectively. These posterior probabilities depend on the prevalence of the disease in question. The methodological problems that arise in the planning of diagnostic studies differ from those encountered in treatment evaluation. This contribution presents an annotated checklist of the most important faults and shortcomings in the planning and the analysis of diagnostic validation studies. Avoiding these deficiencies may help that the study results are accepted by biostatisticians, clinicians and cost units.
Asunto(s)
Ensayos Clínicos como Asunto/estadística & datos numéricos , Técnicas y Procedimientos Diagnósticos/estadística & datos numéricos , Sesgo , Humanos , Reproducibilidad de los Resultados , Proyectos de InvestigaciónAsunto(s)
Fraccionamiento de la Dosis de Radiación , Traumatismos Experimentales por Radiación/etiología , Enfermedades de la Médula Espinal/etiología , Médula Espinal/efectos de la radiación , Animales , Relación Dosis-Respuesta en la Radiación , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Modelos Lineales , Tolerancia a Radiación , Ratas , Ratas Wistar , Efectividad Biológica RelativaRESUMEN
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagnostic validation studies (Phase I to IV). The diagnostic value of a test can be described by indexes like sensitivity, specificity and predictive values. Sensitivity and specificity are so-called nosological probabilities whereas predictive values describe the probabilities of the disease given a positive or negative test result, respectively. These posterior probabilities depend on the prevalence of the disease in question. The methodological problems that arise in the planning of diagnostic studies differ from those encountered in treatment evaluation. This contribution presents an annotated checklist of the most important faults and shortcomings in the planning and the analysis of diagnostic validation studies. Avoiding these deficiencies may help that the study results are accepted by biostatisticians, clinicians and cost units.
Asunto(s)
Técnicas y Procedimientos Diagnósticos/normas , Estándares de Referencia , Reproducibilidad de los Resultados , Proyectos de Investigación , Humanos , Proyectos de Investigación/normasRESUMEN
BACKGROUND: A major problem for children receiving Wilms tumor (WT) chemotherapy is hepatotoxicity, which may even be life-threatening. Dactinomycin (AMD) has been shown to be an important factor, as has abdominal irradiation. PROCEDURE: In the nephroblastoma trial and study SIOP-9 (SIOP-9) two different regimens for the application of AMD were used (standard dose over 3-5 days vs. double dose on a single day). In children at increased risk for local relapse, postoperative abdominal irradiation was given. We analyzed the influence of AMD and radiotherapy on the development of hepatotoxicity in 481 children treated in centers of the German Paediatric Oncology and Haematology Society (GPOH). A special questionaire was sent out for all patients with reduced treatment or delay of more than 1 week because of hepatotoxicity. Because SIOP and the National Wilms Tumor Study (NWTS) used different criteria to asses hepatotoxicity,we applied both definitions. RESULTS: All 72 cases of mild or severe hepatotoxicity occurred during treatment with AMD over 3-5 days with the standard dose (9.4-22.5 microgram/kg/week) compared to none in the group receiving a double dose on 1 day (3.75-8 microgram/kg/week; P < 0.001). Irradiation of the right abdomen, including parts of the liver, enhanced liver toxicity significantly, with a relative risk (RR) of 2.6 (P < 0.003). Preoperative liver toxicity was more frequent in smaller children (P = 0.02) and especially if no dose reduction was done in children with body weight of less than 12 kg (RR 5.3, P = 0.01). If severe liver toxicity was defined according to NWTS criteria, 10% of all treated patients were affected compared to 4.8% if McDonald's criteria for hepatic veno-occlusive disease (VOD) were applied. CONCLUSIONS: To diminish the hepatotoxicity of WT treatment, AMD dose intensity should be reduced (below 10 microgram/kg per week), especially in smaller children or when the liver is irradiated.
Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Dactinomicina/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Hígado/efectos de los fármacos , Tumor de Wilms/tratamiento farmacológico , Adolescente , Antibióticos Antineoplásicos/administración & dosificación , Niño , Preescolar , Dactinomicina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Renales/radioterapia , Masculino , Tumor de Wilms/radioterapiaRESUMEN
On the basis of a survey of the methodological literature, we analyze widespread views on randomization and the advantage of randomized over nonrandomized studies. These views follow from theoretical considerations and at least three types of empirical investigations into the results of published studies. Randomization is often credited with advantages that it does not possess or confer. Several popular theoretical arguments in favor of randomization are shown to be either incorrect or imprecise. The published empirical comparisons of randomized with nonrandomized studies have methodological weaknesses and do not give any convincing information about the value of carefully designed and conducted nonrandomized studies. Six arguments, most of which are pragmatic rather than epistemological, are given to support our belief that randomization should not be avoided without compelling need. We conclude that although there are good arguments in favor of randomization, these are not the ones usually found in the literature. The very negative view on nonrandomized studies sometimes encountered in biostatistics and medicine may be comprehensible from a historical, pragmatic, or educational viewpoint, but it is not well founded on epistemological grounds.