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Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

At least 145 records · Page 8Linked to original sources
PubMed1988

Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling.

Cardiac performance was evaluated at least two years after doxorubicin treatment in childhood in 55 patients without overt congestive cardiomyopathy. None of the patients had received mediastinal irradiation. Computer-assisted analysis of digitised echocardiograms showed impaired rapid diastolic filling and an increased change of dimension between minimal cavity dimension and mitral valve opening. This impairment of diastolic function was related to the cumulative dose of doxorubicin. In contrast when angiotensin II was infused to increase the afterload the end systolic pressure-length and stress-shortening relation indicated normal left ventricular systolic function. But during baseline conditions the end systolic wall stress was significantly increased in patients in whom the cumulative dose of doxorubicin exceeded 360 mg/m2.

Adolescent↗
PubMed1988

Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response.

Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival (MFS) in osteosarcoma, a randomized study was undertaken with the aim of (1) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin (DOX) and cisplatin (CPDD) by administering these drugs postoperatively only after poor response with a milder preoperative regimen, and (2) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively. The available patients were divided into two groups. Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate (HDMTX) and the triple drug combination of bleomycin, cyclophosphamide, and dactinomycin (BCD) and were switched to DOX/CPDD postoperatively in case of poor response. DOX/CPDD was used besides HDMTX for initial treatment in the control arm, and BCD alternatively with CPDD/ifosfamide (IFO) for postoperative salvage treatment. The response rate of the study arm was significantly inferior to the control arm (26% v 60%; P less than .001). The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm (41%); it was unchanged in the control arm (53%) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy (52%). The actuarial 4-year MFS rate of good responders was 73% in the study arm, 79% in the control arm, and not significantly different from that of the COSS-80 study (84%), although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study. The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm (49% v 68%; P less than .1) and also inferior to the COSS-80 study (68%; P less than .01), indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment.

Actuarial Analysis↗
PubMed1988

Infradian biorhythms of enzymuria in man?

The temporal courses of dipeptidyl peptidase IV gamma-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for gamma-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements. These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes.

Adult↗
PubMed1988

[Scintigraphic follow-up of osteosarcoma during neoadjuvant chemotherapy. Results of the cooperative osteosarcoma study of the Society for Pediatric Oncology].

The response of osteosarcomas to preoperative chemotherapy as measured by quantitative 99mTc-diphosphonate scintigraphy was compared with the amount of tumor cell destruction found histologically in the resected specimens. 3-phase bone scintigraphy, with determination of tumor/non-tumor (T/NT) ratios, allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (83%) at the half-way stage of preoperative chemotherapy, when only those tumors were evaluated which showed convergent changes of T/NT ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc-diphosphonate clearance on parametric images predicted correctly the histological tumor response to chemotherapy in 10 of 11 tumors (91%) after completion and in all 11 cases (100%) at the half-way stage.

Adolescent↗
PubMed1987

Histomorphometric changes of osteosarcoma after chemotherapy. Correlation with 99mTc methylene diphosphonate functional imaging.

An investigation to correlate histologic changes in 12 osteosarcoma specimens from patients undergoing chemotherapy was performed using functional images of regional 99mTc methylene diphosphonate (MDP) plasma clearance rates assessed from dynamic bone scintigraphies taken during chemotherapy. Residual tumor cell viability was determined by microscopic examination of multiple thin sections from surgical specimens and quantitated by histomorphometry. Regions that showed decreases in 99mTc MDP plasma clearance of more than 20% were associated with areas of necrotic tumor, and regions that showed absent decline or increasing clearance rates were associated with high residual cell viability and incomplete response to chemotherapy. Therefore, functional bone scintigraphy allows an objective presurgical assessment of tumor response to chemotherapy.

Adolescent↗
PubMed1987

Comparison of quantitative ground substance analysis in biopsy and resected tumour in osteosarcomas.

Osteosarcomas may show variable differentiation. They are divided into osteoblastic, chondroblastic and fibroblastic subgroups depending on their dominant histological differentiation. The pattern of histological differentiation of osteosarcoma is supposed to have an influence on the response to chemotherapy and in this study the relationship between the differentiation of the tumours and response to chemotherapy was examined in 22 osteosarcomas. For this purpose the nuclear size of tumour cells was determined on imprints and the area of the different ground substances on tumour sections after undecalcified preparation. Tumours with little nuclear polymorphism and those with an area of chondroblastic ground substance of more than 20% in the biopsy showed a poor response to chemotherapy. We conclude from our results that lack of nuclear polymorphism and in particular a large area of chondroblastic ground substances in the biopsy, can be regarded as an unfavourable prognostic factor in the response to primary chemotherapy. A comparison of the area of chondroblastic ground substance in biopsy and resection material proves that the biopsy delivers a representative view of the total area of chondroblastic ground substance for the groups of responder and non-responder. Patients with a large amount of chondroblastic ground substance in the biopsy probably require more aggressive chemotherapy.

Adolescent↗
PubMed1987

Hepatic blood flow determination. A comparison of 99mTc-diethyl-IDA and indocyanine green as hepatic blood flow indicators in man.

99mTc-diethyl-acetanilide-iminodiacetic acid (IDA) was compared with indocyanine green (ICG) as an indicator of hepatic blood flow (HBF). Twelve subjects (8 with cirrhosis, 2 with fatty liver, one with pancreatitis, and one with intestinal angina) were studied during hepatic vein catheterization. In 9 subjects the HBF measurements (indirect Fick-principle) were within 0.8-1.9 l/min, and no significant difference was observed between the values obtained by ICG and 99mTc-diethyl-IDA (mean 1.24 vs 1.26 l/min, P greater than 0.4). In 2 subjects with cirrhosis very high but almost identical values were found with the two indicators. In one subject ICG could not be measured in plasma because of hyperlipidaemia, but HBF was easily determined by 99mTc-diethyl-IDA. The results indicate that 99mTc-diethyl-IDA can be used as an indicator of HBF. This indicator is not superior to ICG in patients with decreased liver function, but offers advantages in that it can be used with small plasma samples and permits the determination of HBF in the presence of hyperlipidaemia.

Adult↗
PubMed1987

Indocyanine green plasma clearance as a measure of changes in hepatic blood flow.

The results from simultaneous measurements of indocyanine green (ICG) plasma clearance and hepatic blood flow (HBF) in subjects without hepatic dysfunction during changes in HBF induced pharmacologically or by food stimulation, are reported. A linear relation is established between the relative changes in HBF and that of ICG clearance (r = 0.94), but the changes are not identical, and therefore the changes in HBF cannot be accurately predicted from that of ICG plasma clearance. The reason behind the lack of identity of the changes lies in the complicated kinetics of dye removal by the liver. The hepatic venous catheterization technique is the only method when physiologically correct values for hepatic blood flow or changes therein are wanted.

Adult↗
PubMed1987

Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease.

Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control subjects were studied. Mean hepatic venous oxygen saturation and tension were almost the same in all groups, and hepatic blood flow was inversely correlated to the arteriohepatic venous oxygen difference (r = -0.53, P less than 0.01). Splanchnic oxygen uptake was similar in all groups studied. The arterio-hepatic venous difference of base excess was small and of the same size in all groups, indicating no enhanced production of lactic acid in the liver. Our results do not support the concept that hepatic venous oxygen content is low in alcoholic liver disease and thereby contributes to hypoxic liver damage.

Adult↗
PubMed1987

[Is there a hepatogenic ulcer? Prospective study of the incidence of peptic ulcer in portal hypertension].

During a 7 years study, the endoscopically determined prevalence and incidence of peptic gastroduodenal ulcer in 305 patients with portal hypertension (72% alcoholic cirrhosis, 21.3% non-alcoholic cirrhosis, 6.7% non-cirrhotic portal hypertension) were 4.3% and 3.9% per year, respectively. The yearly risk per patient of suffering from peptic ulcer was 7.4% if both, first and recurrent ulcers (total: 49) were considered. No association was disclosed of peptic ulcer with sex, age, etiology or severity of liver disease. Although an adequate control group was not yet available for comparison, the data do not support the previously postulated relationship between liver cirrhosis and peptic ulcer.

Adolescent↗
PubMed1986

Intermediate-dose methotrexate in the treatment of childhood acute lymphocytic leukaemia: lack of benefit during maintenance therapy following intensive induction therapy.

One hundred and fifty-one children with acute lymphocytic leukaemia (ALL) received multiple agent induction chemotherapy followed by intensive phase treatment. One hundred and thirty-seven patients were randomised for the first year of maintenance treatment to receive reinforcement therapy (pulses) with either intermediate-dose methotrexate (ID-MTX) and prednisone (PRED) or vincristine (VCR) and PRED. The probability of continuous complete remission (CCR) at 5.5 years is 0.80 for the ID-MTX group and 0.84 for the VCR group. Extramedullary relapses were not prevented either in the ID-MTX group nor in the VCR group. Since in previous studies VCR/PRED pulses did not increase CCR rates when given after intensive combination chemotherapy, it can be concluded from this study that neither did ID-MTX reinforcement therapy further improve treatment results in our patients with ALL when given after aggressive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Surgical treatment of pulmonary metastases in childhood.

The curing chance of cancer disseminated to the lungs depends on the global curing chance of that specific tumor, the extent and distribution of its systemic spread and the availability of additional treatment modalities besides surgery. Of all tumors occurring in childhood and adolescence only osteosarcoma, Wilms tumor and Ewing's sarcoma preferentially disseminate to the lungs and such are the most promising candidates for successful treatment. In osteosarcoma with pulmonary dissemination surgical removal of the metastases is indispensable. In Wilms tumor chemoradiotherapy may replace or be used as an adjunct to surgery while in Ewing's sarcoma with primary pulmonary metastases chemoradiotherapy is the treatment of choice. Although metachronous lung metastases may still cured in osteosarcoma and Wilms tumor, they tend to be fatal however in Ewing's sarcoma. A small chance of success itself should not contraindicate metastasectomy but only the actual technically impossible intervention or the definite demonstration of tumor progression no longer controllable of different location. However, even palliative metastasectomy may be indicated in an individual patient.

Adolescent↗
PubMed1986

[Comparative x-ray and nuclear medical studies of osteosarcomas to evaluate the effectiveness of preoperative chemotherapy].

In 16 patients with a long bone osteosarcoma treated after the therapy regimen of COSS 80/82 (Cooperative Osteosarcoma Study) the tumour response to preoperative chemotherapy was assessed by conventional roentgenograms (plain films, tomograms, angiograms). The histological grade of regression determined in the operative specimen was used as a reference for the extent of tumour devitalisation. By their different typical roentgenological course the osteosarcomas with a very good and those with a rather poor response could be correctly identified (100%). On following the clinically used differentiation between "good responders" (histological grades I to III) and "poor responders" (grades IV to VI) the corresponding classification of these tumours by roentgenograms and functional scintigraphic imaging was found to be correct in 94% of the cases. The coincidence of the correct as well as the false results in both radiological methods was as high as 100% if those osteosarcomas showing only a "medium response" in their roentgenograms were added to the clinical group of good responders. There were no fundamentally discrepant results obtained by each of the two radiological techniques. With the combined workup of the roentgenological and the scintigraphic material any incorrect preoperative estimation of tumour regression with a harmful influence on therapy (date and type of surgery, mode of postoperative chemotherapy) could be avoided.

Adolescent↗
PubMed1986

Effect of short lasting hypoxia on the metabolic function of the perfused pig liver. Comparison of ischaemic and hypoxaemic hypoxia.

The effects of hypoxaemia and ischaemia were compared in the perfused pig liver. Decreased hepatic oxygen uptake, galactose elimination, ATP phosphorylation and increased lactate output occurred when the oxygen supply was diminished below 55% of the mean of controls. Below the control limits for oxygen uptake and oxidative phosphorylation, the change in the above variables were correlated to the degree of hypoxia, with no quantitative differences regarding ischaemic or hypoxaemic hypoxia. Galactose elimination was correlated to the ATP concentration (r = 0.81). After 80 min of hypoxia almost complete recovery was seen. It can be inferred from the data that other factors than oxygen diffusion into the liver cells may limit oxidative metabolism. Long and severe hypoxia may be required before irreversible cellular damage occurs in the liver.

Animals↗