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Biomedical subjects

N Graf

Publications and source records attributed to N Graf.

At least 91 records · Page 5Linked to original sources
PubMed1987

Intraspinal mesenchymal chondrosarcoma in a three-year-old boy.

A case is presented of a 3-year-old boy with a mesenchymal chondrosarcoma extending from the 1st to the 5th lumbar vertebra. This is the youngest case of a mesenchymal chondrosarcoma located outside the skeleton or in the C.N.S. After assumed total excision with subsequent radiotherapy and chemotherapy, local tumor recurrence and (later) systemic metastases were detected. Standard therapy should include radical excision because of the high incidence of local recurrence and subsequent radiotherapy because of the expected high incidence of tumor cells in the CSF. The value of chemotherapy cannot be assessed, as it has been applied in only one other case found in the literature.

Cauda Equina↗
PubMed1986

[Behavior of glucosephosphate isomerase in children with malignant diseases].

The normal range of glucose-phosphate-isomerase (GPI) in the plasma of children during the first month of life is up to 80 U/l; until the end of the second year of life between 11 and 50 U/l; thereafter the upper limit is 46 U/l. In osteogenic sarcoma or medulloblastoma there is a good correlation between activity of GPI in plasma and clinical tumor stage. In a lot of other tumors sensitivity of this enzyme is either very low as in Ewing-sarcoma or myeloic leukemia or there is no consistent relation to the extent of the tumor. High activities of GPI are equally obtained in children suffering from cystic fibrosis, diabetes mellitus or muscular dystrophy. GPI is not valid as a tumor marker even being raised in sarcoma and medulloblastoma as mentioned. So it is not necessary to check GPI activity as a part of routine enzyme chemistry.

Adolescent↗
PubMedDate not supplied

Mechanisms of resistance to methotrexate in childhood acute lymphoblastic leukemia: circumvention of thymidylate synthase inhibition.

PURPOSE: In about 25% of patients suffering from acute lymphoblastic leukemia (ALL) treatment failures occur that are most likely due to development of resistance to methotrexate (MTX). Blasts from patients with ALL were evaluated for MTX uptake, formation of long-chain MTX polyglutamates (MTX-Glu5+6), cytotoxicity and thymidylate synthase inhibition by MTX and compared to blasts from patients with acute myelogenous leukemia (AML). METHODS: Radioactively labeled MTX-Glu(n) were analyzed by means of HPLC. Thymidylate synthase activity was measured by a tritium-release assay. Cytotoxicity was determined by trypan blue exclusion. RESULTS: In most ALL blasts (n = 9) large amounts of MTX-Glu5+6 (1.06-7.03 pmol/10(7) cells) and high cytotoxicity (43.5% 92.7%) were found, while in others small amounts of MTX-Glu5+6 (0.0-0.39 pmol/10(7) cells) caused only weak cytotoxicity (6.0% 27.9%) (n = 5, 2 relapsed patients). Resistance to MTX in blasts from AML patients (n = 5) was also caused by reduced synthesis of MTX-Glu5s+6 (0.0-0.42 pmol/10(7) cells). In contrast, some ALL blasts (n = 7, 4 relapsed patients) were able to survive MTX treatment despite large amounts of MTX-Glu5+6 (1.5-5.05 pmol/10(7) cells) and extensive thymidylate synthase inhibition. CONCLUSIONS: Since the majority of ALL patients were examined at first diagnosis, an inherent mechanism of resistance seems most likely. We propose a mechanism based on the switch of thymidylate synthesis to the salvage pathway.

Adolescent↗
PubMedDate not supplied

Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial.

BACKGROUND: Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. METHODS: Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. FINDINGS: By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). CONCLUSIONS: Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health costs.

Adolescent↗
PubMedDate not supplied

Toxicity and effectiveness of high-dose idarubicin during AML induction therapy: results of a pilot study in children.

BACKGROUND: Idarubicin (IDR) is one of the most effective, but also toxic drugs in the treatment of AML. The standard dose used in children and adults is 8-12 mg/m2 during induction. PATIENTS AND METHODS: To improve outcome, we increased the IDR dose from 12 mg/m2 (standard dose in study AML-BFM 93), applied over three days during induction therapy (AIE = Ara-C, Idarubicin, Etoposide) to 14 mg/m2 in a pilot study including 17 patients (16 with de novo AML, one with secondary AML). Outcome and toxicities were compared with the other patients of study AML-BFM 93, treated with 3 x 12 mg/m2 IDR or 6 x 30 mg/m2 daunorubicin (DNR). RESULTS: Patients of the pilot study achieved a good blast cell reduction in the bone marrow on day 15, a high CR rate of 94% and a low relapse rate (3/17 pts.), however, not significantly different to the IDR (12 mg/m2) group. Hematological toxicity was high, median duration until neutrophil recovery > 500/microliter was 25.0 (12-66) days, and similar to the IDR (12 mg/m2) and DNR groups. Duration of thrombocytopenia (time to > 20,000/microliter) was 21 (10-66) days in the pilot study compared to 19 (7-26) days in DNR patients (p = 0.08). Four of 17 pilot patients presented with severe WHO grades 3/4 of mucositis during induction. One patient died in long-lasting aplasia after the 3rd treatment block. CONCLUSION: Results of this pilot study show that the IDR 14 mg/m2 regimen was effective but also toxic. According to our results which, however, are based on small patient numbers, an improved outcome compared to the IDR 12 mg/m2 regimen seems to be unlikely, therefore the possibly increased toxicity might not be acceptable.

Acute Disease↗
PubMedDate not supplied

Obesity after childhood craniopharyngioma--German multicenter study on pre-operative risk factors and quality of life.

BACKGROUND: Craniopharyngiomas are tumorous embryogenic malformations. As the survival rate after craniopharyngioma is high (92 %), prognosis and quality of life (QoL) in survivors mainly depend on adverse late effects such as obesity. PATIENTS AND METHODS: We analyzed 214 children and adolescents with craniopharyngioma. The records of 185 patients (86 %) were available for retrospective analysis of weight profiles and risk factors for obesity. Quality of life (QoL) was measured in 145 patients by the Fertigkeitenskala Münster/Heidelberg score (FMH) and in 77 patients by PEDQOL questionnaire. RESULTS: Eighty-two of 185 patients (44 %) developed severe obesity (body mass index [BMI] > 3 SD). Obese patients were compared with 79 patients (43 %) who kept normal weight (BMI < 2 SD). No differences between obese and normal weight patients were found in terms of gender distribution, age at diagnosis and follow-up period. However, the BMI SDS at the time of diagnosis was higher (p < 0.0001) in patients who developed obesity than in those who did not. Furthermore, obese patients presented with bigger tumors (p < 0.05) and a higher rate of a hydrocephalus requiring a shunt (p < 0.05) and hypothalamic involvement (p < 0.05). The mothers of patients who developed severe obesity had a higher BMI (p < 0.001) at the time of diagnosis. Obese patients had a higher height-SDS at diagnosis (p < 0.05) and at the time of last follow-up (p < 0.05) when compared with normal weight patients. A prediction model for severe obesity after craniopharyngioma was calculated by logistic regression based on the risk factors: patient's BMI > 2 SD at diagnosis (p < 0.05; odds ratio: 16.4), hypothalamic involvement (p < 0.05; odds ratio: 3.4) and maternal BMI > 25 kg/m(2) (p < 0.05; odds ratio: 4.6). Significant increases in BMI (p < 0.001) occurred during the early post-operative period especially during the first three years after diagnosis. FMH percentiles correlated negatively with BMI SDS (Spearman r: - 0.37; p < 0.001). Children with craniopharyngioma rated their QoL more negative (p < 0.05) in regard to physical abilities, cognitive functioning and social functioning when compared with healthy children of the same age group. Severely obese patients with craniopharyngioma estimated their QoL lower (p < 0.05) for all domains except for autonomy, cognition and familial integration in comparison with non-obese patients. CONCLUSION: Hypothalamic tumor involvement and familial disposition for obesity are risk factors for the development of severe obesity in patients with craniopharyngioma. As weight gain starts early after diagnosis and severe obesity causes a reduction in QoL, early therapeutic efforts should be considered in patients at risk. To confirm our results the prospective multicenter study Kraniopharyngeom 2000 on children and adolescents with craniopharyngioma was initiated (www.kraniopharyngeom.com).

Adolescent↗
PubMedDate not supplied

[Telemedicine in pediatric oncology].

UNLABELLED: The telemedicine project of the Competence Net Pediatric Oncology of the German/Austrian Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) has as an initial step of its work-programme sent out a questionnaire to the 54 largest pediatric hematology/oncology units in Germany. Institutions were asked for their experience, motivation, existing infrastructure, and anticipated benefits and obstacles regarding the implementation of telemedicine in patient care and research. Of the 54 largest German Pediatric Oncology institutions asked, 46 completed the questionnaire (85 %). RESULTS: 1. The need for further detailed information on implementation and for help in technical realization of telemedicine applications was expressed by all participants. 2. The majority expected practical advantages from telemedicine communication and anticipated that telemedicine will increase quality in treating children with cancer. 3. Expert consultation (study chairman, reference radiologists) is stated as to be most important. 4. Thirty-three of 46 physicians (72 %) believe that telemedicine will reduce costs in medical care within the next years. 5. It is anticipated that the introduction of telemedicine is time consuming. 6. The lack of available medical informatics competence and manpower was regarded as the most important obstacle. 7. Data security and standardization, transfer speed and transmission quality are considered most important. 8. Most of the institutions (91 %) use computers in the management of patients. Fourty-four (96 %) are connected to the Internet. 9. Thirty-seven of 46 institutions were prepared to invest in the implementation of telemedicine. This analysis demonstrates that the use of telemedicine is expected to become standard in pediatric oncology, while the existing infrastructure and status of information regarding this subject at present are insufficient. The most pressing practical need for telemedicine applications is seen in the field of electronic expert consultation. Hence, the Telemedicine-Project of the GPOH Competence Net will focus on this aspect first.

Attitude of Health Personnel↗
PubMedDate not supplied

[The importance of conventional radiographs in the diagnosis of osteosarcoma].

We report about a 12-year-old boy with a history of recurrent patella luxation. Due to persistent pain in the distal left femur a MRI examination was performed in another hospital which suggested a malignant bone tumor. Without validation of the MRI findings by conventional radiographs bone biopsy was performed. Histopathological examination yielded the diagnosis of a chondroblastic osteosarcoma. Before initiating polychemotherapy, plain radiographs for the first time, a nuclear imaging study and an additional MRI examination were performed in our hospital. The results of these studies made the diagnosis of an osteosarcoma unlikely. In particular, plain radiographs did not show any osseous lesion which was characteristic of an osteosarcoma. To establish a definite diagnosis biopsy was repeated with resection of the bone area which showed suspicious changes in MRI studies. An osteosarcoma was ruled out by histopathological examination. The pathologic changes detected in MRI were rated as bone bruise on plain radiographs and seemed to be of traumatic origin. Our case report emphasises the importance of conventional radiographs in establishing the diagnosis of an osteoarcoma respectively bone tumors and tumor-like lesions in general. They still remain the mainstay in diagnosing bone forming tumors. MRI imaging studies may show changes which mimick solid lesions but in deed can be of traumatic origin. Without informing the pathologist about the exact origin of the specimen, histopathological examination may lead to the misdiagnosis of a chondroblastic osteosarcoma if specimen, like in this case report, represents epiphyseal tissue showing cartilaginous areas with reactive bone formation.

Biopsy↗
PubMedDate not supplied

[Eye findings in paediatric brain tumour - data basis for a follow-up proposal].

BACKGROUND: Morphologic alterations and functional disturbances of the visual system are frequently observed in children with brain tumours. At present we are not aware of published data giving recommendations for ophthalmic follow-up in these patients. PATIENTS: A retrospective analysis of 125 children with a brain tumour was done to perform a risk analysis. METHOD: According to a sequential test strategy risk factors for various eye findings have been evaluated. RESULTS: Tumour location is the major risk factor for ophthalmological findings. Eye motility pathology was mainly associated with tumour invasion of the brain stem, grade of malignancy, and mass effects and occurred mainly in those patients with the presence of visual system symptoms as the leading symptom at the time of diagnosis. VEP alterations were a frequent sign in any group of brain tumours. CONCLUSIONS: As a follow-up for children with brain tumour, we recommend to perform an ophthalmologic examination at the time of diagnosis, before and after any neurosurgery, radiotherapy and chemotherapy respectively. During chemotherapy controls should be performed every 3 months. After the end of treatment the patients should be seen by an ophthalmologist at least once a year lifelong. For some well defined risk populations, we recommend more frequent controls. Visual Evoked Potentials and perimetry ought to be performed in any child at diagnosis, and more often in defined risk patients.

Adolescent↗