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Biomedical subjects

D Schuler

Publications and source records attributed to D Schuler.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Chronic granulomatous disease (CGD): dysfunction of the neutrophil granulocyte NADPH-oxidase enzyme system].

Dysfunction of NADPH oxidase results in chronic granulomatous disease (CGD), a syndrome characterized by severe bacterial and fungal infections. Phagocytes of the patients are unable to kill ingested microorganisms which leads to the formation of granulomas and abscesses. Predominant pathogens are the catalase-positive bacteriae (Staphylococcus aureus) and some fungi (Aspergillus species). Infections of these patients should be treated by antimicrobial agents, which penetrate cells and kill pathogens inside. The aim of this study was to give a short description of the structure and function of the NADPH oxidase enzyme and to summarize the results obtained during the diagnostic of 10 patients with chronic granulomatous disease. Characterization of the disease was confirmed by mutation analyses.

Common Variable Immunodeficiency↗
PubMed1997

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P-postlabeling and electrochemical detection.

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P-postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

[In vivo effect of etoposide on the pharmacokinetics of methotrexate].

High dose (5 g/m2/24 h) methotrexate therapy was combined two times with etoposide (100 mg/m2/1h) infusions as a part of the Medulloblastoma protocol developed in our Department Vepesid therapy was administered in two different schedules. The first group of the patients have received etoposide immediately before and at the end (24th h) of methotrexate treatment. The second group was treated with etoposide at 24 h and at 48 hour after starting methotrexate infusion. In this latter group treatment related grade 3-4 toxicity developed more frequently than in the first group (58.6% vs 33.3%). The authors observed that after the second dose of etoposide given at 48 h (second group) both total and unbound serum methotrexate levels (determined by high performance liquid chromatography) were elevated by 53.14-109.19%, and 25.86-64.95%, respectively by the third hour after completion of Vepesid infusion. This effect was detectable for 6 hours. All the liver and kidney functions of the patients were in the normal range. These results suggest the possibility of partial recirculation of extra/intracellular methotrexate into the blood after etoposide administration. Based on these results the therapeutic protocol has been modified and Vepesid is given prior to and at the end (24 h) of high dose methotrexate treatment. Under these conditions only a slight decrease of methotrexate elimination has been detected between the 25-28th h. These results emphasize the role of possible schedule dependent interactions of cytostatic drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Immunophenotyping of childhood leukemias--results of the first 100 bone marrow tests].

The authors used a cell-surface-marker analysis by flow cytometry for immunophenotyping of pediatric leukemia from 1993. Results of their first one-hundred cases were summarized. They examined 68 bone-marrow samples from 58 patients affected by leukemia, and diagnosed 19 acute myeloid leukemia (32%), 5 T-cell acute lymphoid leukemia (8%), 32 B-cell acute lymphoid leukemia (54%) and 2 biphenotypic leukemia (5%). A higher CD34 antigen positivity was found compared to adults. They analysed the incidence and prognostic significance of myeloid + lymphoid leukemia and lymphoid + myeloid leukemia cases. Nondiagnostic and unsuccessful cases were got according to the literature.

Adolescent↗
PubMed1996

Diffuse plasmacytosis in a child with brainstem glioma following multiagent chemotherapy and intensive growth factor support.

The use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to abrogate chemotherapy-induced neutropenia has become a routine part of many cancer treatment regimes. However, there are still very few data available about possible complications related to repeated or prolonged use of these agents in patients with malignant solid tumors. The authors report a child with brainstem glioma who received repeated cycles of multiagent chemotherapy with G- or GM-CSF support. During this period of 10 months, no clinical side effects were observed that could have been attributed to growth factor administration. However, postmortem histological examination revealed the presence of diffuse plasmacytosis, a rare hematological disorder in childhood. Undifferentiated plasma cells of nonmonoclonal origin could be demonstrated infiltrating bone marrow, lungs, and lymph nodes of the patient. Based on previously published in vitro and in vivo evidence on the interleukin-6 (IL-6)-mediated stimulatory effect of G- and GM-CSF on myeloma cell proliferation, the authors suggest a possible link between extensive growth factor support and the development of plasmacytosis in this patient.

Adolescent↗
PubMed1996

SIOP Working Committee on Psychosocial issues in pediatric oncology: guidelines for care of long-term survivors.

This is the third official document of the SIOP Working Committee on Psychosocial issues in pediatric oncology constituted in 1991. This document develops another topic already discussed and approved by the SIOP committee. The topic: "Care of long-term survivors" is addressed to the pediatric oncology community as guidelines that could be followed for considering this issue in a more appropriate way.

Adolescent↗
PubMed1996

Childhood leukaemia in Europe after Chernobyl: 5 year follow-up.

The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.

Child↗
PubMed1996

Action profiles of predictors of death and survival time in stage I malignant melanoma.

BACKGROUND: Many studies have been performed to identify prognostic factors of malignant melanoma using multivariate regression models. In these models, it is generally assumed that quantitative predictors such as age or tumor thickness enter linearly into the model, or they are categorized. OBJECTIVE: The purpose of the present study is to investigate possible curvature (nonlinearity) of predictors of 'death from MM within 5 years after diagnosis' and 'survival time after diagnosis' avoiding the known shortcomings of categorizing predictors. METHODS: Our analyses are based on data of 677 patients with stage I melanoma of the skin collected at the Cancer Registry of the Canton of Zurich. In order to study non-linearity of predictors, we use 'generalized additive models' (GAM): in a GAM the usual prognostic index is replaced in an optimal way by a more flexible form where the individual linear terms are replaced by possibly curved functions of the predictors. Plotting the corresponding curves (the 'action profiles') allows one to visualize easily the shape by which predictors 'act' over the whole range of values. RESULTS: Essentially the same results emerged when studying 'death from melanoma' and 'survival time in melanoma': age and tumor thickness have a pronounced nonlinear association with both endpoints taking simultaneously into account effects of sex and tumor site. The action profile for age is J or U shaped. The action profile for thickness has a 'two-phase' pattern. It increases linearly for low thickness values and flattens for higher values. The shape of the action profiles was checked by performing a Monte Carlo simulation ('boot-strapping'). CONCLUSIONS: The best prognosis of melanoma was found within a middle age range while younger and older patients showed a poorer prognosis. In our data, the increase in thickness in the range above 2 mm is of much less clinical relevance than in the range below 2 mm. GAMs may be of great value for clinicians in providing a visualization of the shape by which predictors act and to obtain a better understanding of the complex relationships between predictors and survival. Not considering curvature of action profiles may result in excluding relevant predictors.

Adult↗
PubMed1996

Crotonaldehyde: a carcinogenic and mutagenic air, water and food pollutant.

Crotonaldehyde is mutagenic and carcinogenic and it is ubiquitous in our environment. The data base does, however, not allow an assessment of the carcinogenic risk. We have developed a sensitive 32P-postlabelling technique which allows the detection of specific DNA-adducts in animal tissues as markers for initiation of cancer cells. Adducts were found in several organs of F 344 rats after gavage and persisted to a certain extent. The determination of adduct levels in animal tissues after different exposure or even in human tissues can therefore be considered as an effect monitoring and would certainly improve the risk assessment.

Air Pollutants↗
PubMed1995

Response of untreated stage IV Wilms' tumor to single dose carboplatin assessed by "up front" window therapy.

A total of nine children with previously untreated stage IV Wilms' tumor of favorable histology were treated according to the Austrian/Hungarian Wilms' Tumor Protocol 89 and received a preoperative single dose of carboplatin as an "up front" window therapy. The treatment consisted of carboplatin as a single-dose of 600 mg/m2 over 30 minutes on day 1. Response evaluation by chest X-ray, serial CT scans, and sonography was performed on day 22. Investigation of the abdominal tumors revealed seven partial responses (78%), one nonresponse, and one progressive disease with a median tumor volume reduction of 62%. Response of metastases evaluated by CT scans was as follows: four complete remission, four partial response, and one nonresponse. Thrombocytopenia (WHO grade III 1, grade II 2, grade I 2) and leukocytopenia (WHO grade II 1, grade I 5) were the main side effects. No renal or liver toxicity were observed. The overall response rate after a preoperative single-dose of 600 mg/m2 carboplatin in untreated patients with stage IV Wilms' tumor is encouraging and the toxicity acceptable. This data indicate that carboplatin seems to be an additional effective drug in patients with previously untreated Wilms' tumor of favorable histology.

Austria↗
PubMed1995

Safety and efficacy of meropenem in hospitalised children: randomised comparison with cefotaxime, alone and combined with metronidazole or amikacin. Meropenem Paediatric Study Group.

In this multicentre, randomised study of 170 children hospitalised with bacterial infections, meropenem (10 to 20 mg/kg every 8 h) was found to be as effective and as well tolerated as cefotaxime (100 to 150 mg/kg/day), with or without amikacin or metronidazole. Most drug-related adverse events were mild and self-limiting. Neither regimen was associated with seizures. The overall incidence of clinically significant laboratory changes was similar in the two treatment groups. Satisfactory clinical responses were obtained in 94/96 (98%) patients treated with meropenem monotherapy and 43/46 (93%) children treated with cefotaxime regimens, while satisfactory bacteriological responses were obtained in 25/28 (89%) and 9/10 (90%) patients, respectively. Meropenem monotherapy appears to be a well-tolerated and effective drug for paediatric infections.

Amikacin↗
PubMed1994

[Pharmacokinetic study of dibromodulcitol in children with brain tumors].

Systemic pharmacokinetics of high-dose (500 mg/m2), orally administered dibromodulcitol (Elobromol) were studied in 16 chemotherapeutic courses administered to 5 patients. Cerebrospinal fluid dibromodulcitol levels were also analysed in two patients. Bromoepoxydulcitol, dianhydrodulcitol are cytotoxic, whereas bromoanhydrodulcitol, andhydroepoxydulcitol are inactive metabolites detectable during the biotransformation of dibromodulcitol. The HPLC method, developed by our team, is suitable for the determination of both dibromodulcitol and its main metabolites (dianhydrodulcitol and bromoanhydrodulcitol). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexite-derivatives in pediatric patients. With the exception of one patient, concentration-time curves were analysed by the one-compartment model. From the 30th minute following administration, dibromodulcitol was detectable in all plasma samples for at least 12 hours, its concentration however was usually undetectable by the 24th hour. Though highly variable in value, dianhydrodulcitol concentrations were detectable during all but one therapeutic courses. The following peak concentrations were observed: dibromodulcitol: 3.46-30.63 microM; dianhydroldulcitol: 1.70-6.17 microM; bromoanhydrodulcitol: 0-5.63 microM. The correlation of area under the curve for bromoanhydrodulcitol and dibromodulcitol was exponential up to 200 microMxh with no additional increase detectable above this limit; the distribution of dianhydrodulcitol values were described by a maximum-curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives were detectable in the cerebrospinal fluid even if the concentration of the individual metabolite remained undetectable in plasma. The cerebrospinal fluid concentrations of dibromodulcitol were almost constant in the period from 2.5 to 8 hours following administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Neurologic complications of childhood malignancies].

The authors summarize the neurological complications of childhood malignancies based on their own experiences and review of the literature. The clinical features, the diagnostic methods of choice and the therapies are listed briefly.

Brain Diseases↗
PubMed1994

Pharmacokinetic studies on Elobromol in children with brain tumors.

Systemic pharmacokinetics of high dose (500 mg/m2), orally administered Elobromol (dibromodulcitol, DBD) were studied in 16 chemotherapeutic courses administered to five patients. Cerebrospinal fluid (CSF) DBD levels were also analyzed in two patients. Bromoepoxydulcitol (BED), dianhydrodulcitol (DAD) are cytotoxic, whereas bromoanhydrodulcitol (BAD) and anhydroepoxydulcitol (AED) are inactive metabolites detectable during the biotransformation of DBD. The HPLC method, developed by our team, is suitable for the determination of both DBD and its main metabolites (DAD and BAD). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexitol derivatives in pediatric patients. With the exception of one patient, concentration time curves were analyzed by the one-compartment model. From 30 min following administration, DBD was detectable in all plasma samples for at least 12 h; its concentration, however, was usually undetectable by 24 h. Though highly variable in value, DAD concentrations were detectable during all but one of the therapeutic courses. The following peak concentrations were observed: DBD = 3.46-30.63 microM, DAD = 1.70-6.17 microM and BAD = 0-5.63 microM. The correlation of AUCBAD and AUCDBD values were exponential up to 200 microM h with no additional increase detectable above this limit: the distribution of AUCBAD and AUCDBD was described by a maximum curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives was detectable in CSF even if the concentration of the individual metabolite remained undetectable in plasma. DBD CSF concentrations were almost constant in the period from 2.5 to 8 h following administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

[Poly-electrolyte fractionated porcine factor VIII in the treatment of hemophilia A].

In approximately 10 to 15 percent of congenital hemophilia A patients circulating antibodies to factor VIII appear in the blood that poses a serious problem in their treatment. A number of methods and preparations are used in the clinical practice to overcome this problem. Authors report their favourable clinical experience with the administration of polyelectrolyte-fractionated porcine factor VIII. concentrate in a hemophiliac child for the first time in Hungary and a brief review of the clinical methods in use in the management of factor VIII. inhibitors.

Animals↗
PubMed1993

[First experience with the use of granulocyte-macrophage colony stimulating factor in pediatric oncology].

Authors report their first experiences with the application of granulocyte-macrophage colony stimulating factor in 12 pediatric cancer patients (14 cases). The drug was given in a 5 micrograms/kg single daily dose subcutaneously. Patients were divided into three main indication groups: 1. Severe neutropenia (white blood cell count < 1.0 G/l) and sepsis (6 patients); 2. Prolonged neutropenia (white blood cell count: 1.0-2.0 G/l) and delay in treatment (3 patients); 3. Dose-escalation of chemotherapy in therapy-resistant cases (4 patients). Authors report that in all cases a substantial raise in white blood cell count could be achieved after 5-6 days of granulocyte-macrophage colony stimulating factor treatment. No side effects were detected except of a moderate local pain at the site of the injection. Authors suggest that in the above described dose and way of administration granulocyte-macrophage colony stimulating factor can be an effective agent in the treatment of chemotherapy-induced neutropenia in paediatric oncology.

Adolescent↗
PubMed1993

[Use of ondansetron, a 5-HT3 receptor antagonist, as a new type of antiemetic in pediatric oncology].

The effectiveness of the new antiemetic drug, the 5-hydroxytryptamin (5-HT) receptor antagonist ondansetron was evaluated in paediatric cancer patients. 5-HT3 antagonists represent a new class of drugs effective in the control of chemo- and radiotherapy-induced emesis. Based on their selectivity 5-HT3 antagonist are free from extrapyramidal side effects, a major problem in children in the case of currently used dopamine receptor antagonists (e.g. metoclopramide). In this study ondansetron was tested as antiemetic in 33 children with malignant disease (132 chemotherapy cycles) treated with: 1. high-dose cisplatin (120 mg/m2), 2. intermediate-dose cisplatin (60 mg/m2) and 3. no cisplatin-containing, combined high-dose chemotherapy. Ondansetron was found to be safe and effective in the control of acute and delayed emesis in all treatment groups. Its effectiveness was superior to the currently used antiemetic drugs in the period of acute emesis.

Adolescent↗