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1.
Biotechnol Rep (Amst) ; 39: e00805, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37448785

ABSTRACT

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.

2.
Environ Monit Assess ; 191(6): 387, 2019 May 21.
Article in English | MEDLINE | ID: mdl-31115704

ABSTRACT

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.


Subject(s)
Diatoms/metabolism , Environmental Monitoring/methods , Industrial Waste/analysis , Phytoplankton/metabolism , Plants/metabolism , Rivers/chemistry , Water Pollution/adverse effects , Water Pollution/analysis , Ammonia/analysis , Biodiversity , Cyanobacteria/classification , Cyanobacteria/metabolism , Ecosystem , Euglenida/metabolism , Oxygen/analysis , Phosphates/analysis , Plants/classification , Turkey , Water Quality
3.
Klin Padiatr ; 224(6): 398-403, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22915450

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/administration & dosage , Histone Deacetylase Inhibitors/administration & dosage , Hydroxamic Acids/administration & dosage , Leukemia/drug therapy , Lymphoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasms/drug therapy , Administration, Oral , Adolescent , Antineoplastic Agents/pharmacokinetics , Child , Child, Preschool , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Histone Deacetylase Inhibitors/pharmacokinetics , Humans , Hydroxamic Acids/pharmacokinetics , Leukemia/blood , Long-Term Care , Lymphoma/blood , Male , Neoplasm Recurrence, Local/blood , Neoplasms/blood , Vorinostat
4.
Environ Sci Pollut Res Int ; 19(7): 2983-93, 2011 Aug.
Article in English | MEDLINE | ID: mdl-22374187

ABSTRACT

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.


Subject(s)
Chromium/metabolism , Microalgae/metabolism , Water Pollutants, Chemical/metabolism , Adsorption , Alginates/chemistry , Biodegradation, Environmental , Chromium/chemistry , Gelatin/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Kinetics , Metals, Heavy/chemistry , Metals, Heavy/metabolism , Microalgae/ultrastructure , Surface Properties , Thermodynamics , Water Pollutants, Chemical/chemistry , Water Purification
6.
Article in German | MEDLINE | ID: mdl-19326057

ABSTRACT

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.


Subject(s)
Clinical Trials as Topic/legislation & jurisprudence , Diagnostic Tests, Routine/methods , Biomarkers, Tumor/blood , Clinical Trials as Topic/methods , Diagnostic Tests, Routine/statistics & numerical data , Germany , Humans , Mass Screening/legislation & jurisprudence , Mass Screening/methods , Mass Screening/statistics & numerical data , Neoplasms/blood , Neoplasms/diagnosis , Predictive Value of Tests , ROC Curve , Research Design/legislation & jurisprudence , Research Design/statistics & numerical data
7.
J Pathol ; 211(3): 314-22, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17152048

ABSTRACT

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.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genes, p16 , Genes, p53 , Head and Neck Neoplasms/genetics , Microarray Analysis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/genetics , Gene Deletion , Gene Expression , Head and Neck Neoplasms/mortality , Humans , Hypopharyngeal Neoplasms/genetics , Hypopharyngeal Neoplasms/mortality , Immunohistochemistry/methods , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/mortality , Mouth Neoplasms/genetics , Mouth Neoplasms/mortality , Mutation , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/mortality , Survival Rate
9.
Z Gastroenterol ; 43(4): 357-65, 2005 Apr.
Article in German | MEDLINE | ID: mdl-15830301

ABSTRACT

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.


Subject(s)
Aftercare/statistics & numerical data , Colorectal Neoplasms/surgery , Neoplasm Recurrence, Local/epidemiology , Neoplasms, Second Primary/epidemiology , Patient Compliance/statistics & numerical data , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Colonoscopy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Diagnostic Imaging , Female , Follow-Up Studies , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Male , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging , Neoplasms, Second Primary/diagnosis , Patient Dropouts/statistics & numerical data , Predictive Value of Tests , Survival Rate
10.
Article in German | MEDLINE | ID: mdl-15249749

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Mistletoe , Phytotherapy , Plant Extracts/therapeutic use , Randomized Controlled Trials as Topic/standards , Female , Humans , Plant Preparations/therapeutic use , Plant Proteins/therapeutic use , Prospective Studies , Ribosome Inactivating Proteins, Type 2 , Time Factors , Toxins, Biological/therapeutic use
11.
Ann Oncol ; 15(5): 808-20, 2004 May.
Article in English | MEDLINE | ID: mdl-15111352

ABSTRACT

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 (

Subject(s)
Kidney Neoplasms/therapy , Neoplasm Recurrence, Local , Wilms Tumor/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Male , Morbidity , Neoplasm Staging , Prognosis , Risk Factors , Wilms Tumor/pathology
13.
Ann Oncol ; 12(3): 311-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11332141

ABSTRACT

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.


Subject(s)
Kidney Neoplasms/pathology , Wilms Tumor/pathology , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Dactinomycin/administration & dosage , Female , Humans , Infant , Infant, Newborn , Kidney Neoplasms/classification , Kidney Neoplasms/drug therapy , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Risk Factors , Survival Analysis , Treatment Outcome , Vincristine/administration & dosage , Wilms Tumor/classification , Wilms Tumor/drug therapy
14.
Clin Anat ; 13(6): 429-33, 2000.
Article in English | MEDLINE | ID: mdl-11111894

ABSTRACT

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.


Subject(s)
Epidermis/anatomy & histology , Fingers/anatomy & histology , Adolescent , Adult , Diabetes Mellitus/pathology , Female , Humans , Male , Middle Aged , Sex Factors
15.
Int J Radiat Oncol Biol Phys ; 48(1): 95-103, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10924977

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Analysis of Variance , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Dose Fractionation, Radiation , Esophagitis/etiology , Female , Humans , Karnofsky Performance Status , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Palliative Care , Prospective Studies , Radiation Pneumonitis/etiology , Regression Analysis , Survival Rate , Time Factors
16.
Med Klin (Munich) ; 95(1 Spec No): 54-60, 2000 May.
Article in German | MEDLINE | ID: mdl-10851849

ABSTRACT

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.


Subject(s)
Clinical Trials as Topic/statistics & numerical data , Diagnostic Techniques and Procedures/statistics & numerical data , Bias , Humans , Reproducibility of Results , Research Design
17.
Med Klin (Munich) ; 94(9): 522-9, 1999 Sep 15.
Article in German | MEDLINE | ID: mdl-10544616

ABSTRACT

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.


Subject(s)
Diagnostic Techniques and Procedures/standards , Reference Standards , Reproducibility of Results , Research Design , Humans , Research Design/standards
19.
Med Pediatr Oncol ; 33(5): 462-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10531570

ABSTRACT

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.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Dactinomycin/adverse effects , Kidney Neoplasms/drug therapy , Liver/drug effects , Wilms Tumor/drug therapy , Adolescent , Antibiotics, Antineoplastic/administration & dosage , Child , Child, Preschool , Dactinomycin/administration & dosage , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Infant , Kidney Neoplasms/radiotherapy , Male , Wilms Tumor/radiotherapy
20.
J Clin Epidemiol ; 52(6): 487-97, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10408986

ABSTRACT

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.


Subject(s)
Epidemiologic Studies , Random Allocation , Randomized Controlled Trials as Topic/standards , Causality , Humans
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