Biomedical subjects
K Winkler
Publications and source records attributed to K Winkler.
[The suitability of selected humic acid batches as culture media additives for isolating thermophilic Campylobacter species].
Using freshly poured respectively five days under light and air stored Campylobacter media blood or lignite humic acids containing Mueller-Hinton-Agar proved to be better for isolation of a Campylobacter field strain than unsupplemented or peat humic acids containing media. The observed differences between the used media are probably caused by three different ability to prevent the accumulation of a photochemically induced toxicity by storing of media under light and air. The storage of blood respectively lignite humic acids containing media over fourteen days under dark and air leads to a time and trend dependent decrease of the colony counts of the Campylobacter field strain. By means of equations of spline functions the observed decrease in ability of media to support the growth of thermophilic Campylobacter can be described mathematically. By using the mathematical model the theoretical extend of growth of Campylobacter on the media can be determinate with respect to the applied inoculum and to the time of storage of media. The cause of decrease in the isolations rate with respect to the time of storage and the cause of different effectiveness of the used humic acids in the media are discussed.
Parametric imaging of 99mTc methylene diphosphonate biokinetics in osteosarcoma for preoperative evaluation of chemotherapy-induced necrosis.
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The potential of MRI in preoperative evaluation of chemotherapy-induced necrosis in osteosarcoma and Ewing's sarcoma.
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Morphological investigation of tumor growth and distribution of viable tumour areas in osteosarcomas after chemotherapy.
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Intensified chemotherapy with ifosfamide (IFO) and influence of intraarterial (i.a.) versus intravenous (i.v.) infusion of cisplatinum (DDP). Preliminary results.
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Surgical margins in osteosarcoma.
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[Liver scintigraphy as a diagnostic adjuvant to ultrasonic examination in cases of hepatic focal processes].
The object of this work was to investigate whether the decline in employing hepatic scintigraphy reflects the lack of significance attached to this method in investigation of focal disease of the liver. A retrospective study was performed on 693 patients in whom hepatic ultrasound examination was performed during the year 1986. Seventy-eight of these patients were submitted to supplementary hepatic scintigraphy. Hepatic scintigraphy provided supplementary information in 10% (70/693) of all ultrasound examinations of the liver. Hepatic scintigraphy is therefore recommended as a supplementary examination to ultrasound examination in cases of focal disease of the liver when the latter has yielded ambiguous information or cannot be performed for technical reasons.
High-dose ifosfamide with mesna uroprotection in Ewing's sarcoma.
The German Society of Pediatric Oncology (GPO) has studied the efficacy of high-dose ifosfamide with mesna uroprotection in patients with Ewing's sarcoma. A phase II trial of ifosfamide (IFO) (2 g/m2 per day, days 1-5) in eight patients with recurrent evaluable disease resulted in three partial and two complete responses lasting from 3 to 12 months (median, 6 months). In a second phase II trial in 15 patients, the combination of IFO and cisplatin (20 mg/m2 per day, days 1-5) resulted in 7 partial and 2 complete responses lasting from 3 to 32 months (median, 6 months). Consequently, in 1985 IFO was incorporated into first-line chemotherapy for newly diagnosed patients (replacing cyclophosphamide) and given in combination with vincristine, actinomycin D, and adriamycin (VAIA) in patients considered to be at high risk for relapse. IFO was given at a dose of 3 g/m per day on days 1 and 2 as a 48-h continuous infusion, in combination with actinomycin D (0.5 mg/m2 per day on days 1-3) or Adriamycin (30 mg/m2 per day on days 1 and 2). The study was piloted from March to December 1985 and has been open since January 1986; 37 patients were entered during the pilot phase and 65 have been entered in the ongoing main trial since January 1986. At present, Kaplan-Meier disease-free survival projects that disease-free survival in patients with large primary tumors has improved compared with that reported for the previous CESS 81 trial. The toxicity of the VAIA regimen was comparable with that of the conventional vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) regime used in the previous CESS 81 trial.
Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma. Cooperative Osteosarcoma Study Group COSS.
Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Tumors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.
Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy.
The risk of congestive heart failure restricts the clinical use of doxorubicin to cumulative doses of 450-550 mg/m2, when it is given using high-dose rapid intravenous application. As the high peak serum levels which follow rapid administration seem to be correlated with cardiotoxicity, application schedules leading to lower peak serum concentrations have been developed. This paper reviews the influence of those schedules on cardiotoxicity, non-cardiac toxicities, pharmacokinetic data and antineoplastic efficacy. While the reduction of cardiotoxicity by long-term application schedules is well documented, much less can be said about the antitumor effect of those schedules. Controlled studies dealing with this problem are needed. This review provides a base for that purpose.
Centralized diagnosis and treatment of bone and soft tissue tumors.
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[Extreme hyperphosphatemia with hypocalcemia within the scope of cell lysis syndrome in a child with T-ALL].
In a 10 3/4-year-old girl suffering from a T-ALL with an extremely high leukocyte blood cell count (400,000/microliters) we observed a tumor-lysis syndrome with hyperphosphatemia and hypocalcemia accompanied by clinical signs of tetany. The therapeutic application of calcium gluconate resulted in vascular calcification by exceeding by far the calcium-phosphate solubility product. The fast lysis of T-lymphoblasts with their high phosphate concentration is etiologically involved in the hyperphosphatemia. Our patient died of multiorganic failure. Regular monitoring of phosphate in urine might be helpful in instituting early therapeutic procedures.
[Results of treatment in primary disseminated osteosarcoma. Analysis of the follow-up of patients in the cooperative osteosarcoma studies COSS-80 and COSS-82].
Since the long-term disease-free survival rate in adjuvantly treated osteosarcoma has nowadays reached a level of about 70%, increasing interest is also being directed towards primarily disseminated forms of the disease. Primary metastases, which were confined to the lungs in 42 cases, were detected in 59 out of 421 patients from the prospective therapy trials COSS-80 and COSS-82. The primary tumors were more frequently localized in the proximal femur and flat bones as compared to patients without detectable metastases at diagnosis. Following chemotherapy and surgery of the primary tumor, 15/31 (48%) patients whose metastases were excised have survived for 4-8 years, in contrast to only 1/22 (5%) of those patients whose metastases could not be removed for a variety of reasons. Clinical or histological evidence of tumor response after primary chemotherapy significantly influenced the outcome of the metastasectomized patients.
Ifosfamide in pediatric malignancies.
In pediatric malignancies, particularly sarcomas, alkylating agents play an important role in the curative, combination chemotherapy approach. Since high doses of ifosfamide, the structural isomer of cyclophosphamide, were made tolerable with mesna uroprotection, high-dose ifosfamide (5 to 10 g/m2) has replaced conventional-dose cyclophosphamide (900 to 1,500 mg/m2) in some combination chemotherapy regimens. In Ewing's sarcoma and soft tissue sarcoma, the response rate and proportion of patients surviving disease free have been increased (at least for poor-prognosis patients) by 15% to 20% with an ifosfamide-containing regimen, as used in ongoing trials of the German Society of Pediatric Oncology. In germ cell tumors, the combination of ifosfamide and etoposide has proved to be an effective salvage regimen in patients resistant to vinblastine, bleomycin, and cisplatin. In stage IV disseminated neuroblastoma, however, the introduction of ifosfamide-containing regimens has not altered the poor prognosis. Results reflecting the value of ifosfamide in osteosarcoma, Wilms' tumor and Hodgkin's and non-Hodgkin's lymphomas are pending. It is not yet known whether high doses of akylating agents will increase the risk of late sequelae in cured patients.
Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients.
The clinical presentation of the disease and the results of treatment in 42 patients with malignant peripheral neuroectodermal tumors (MPNT) entered into the Cooperative Ewing's, soft tissue, and neuroblastoma trials of the German Society of Pediatric Oncology were retrospectively analyzed. Within the Ewing's sarcoma trial, patients with chest wall lesions were particularly analysed for MPNT features. The period of observation ranged from 15 to 86 months; the median relapse-free time was 24 months. There were 28 male and 14 female patients, the median age of patients was 15 years (range, 9 months-23 years). Thirty-two patients had localized disease (M0), and ten patients presented with primary metastases (M1). The predominant location of the tumors was the thoracopulmonary region, followed by the extremities, the abdominal/pelvic, and head and neck region. Thirty-one of 42 tumors involved the adjacent bone. The disease-free survival according to Kaplan-Meier life-table analysis was 56% +/- 11% for Stage M0 patients at 3 years. Nine of ten patients with M1 disease showed progression of their disease. Most patients had combined modality treatment with surgery, chemotherapy and radiation therapy. Best results were obtained with extensive surgery. Radiation doses ranged from 20 to 60 Gy and could not be correlated with the outcome of the disease. Most recurrences occurred at the site of the primary tumor. In patients with primary chemotherapy after biopsy-proven diagnosis, the responsiveness of this disease to chemotherapy could be demonstrated. Combination chemotherapy containing anthracyclines and high doses of alkylating agents appeared superior.
Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial.
The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3-year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewing's sarcoma of bone.
Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females.
During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.