Search PubMed⌕ Search

Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

At least 163 records · Page 9Linked to original sources
PubMed1986

The effect of physiological temperature changes on the galactose elimination capacity of the isolated perfused pig liver.

The effect of temperature changes (36-40 degrees C) on the liver function was studied in the isolated perfused pig liver. When compared with control studies no effect was observed on lactate, glucose, bile flow, ATP and energy charge, and the recovery after the changes in temperature was complete. The only significant changes observed regarded the hepatic oxygen uptake and galactose elimination capacity. The increase of 1 degree C resulted in an increase in galactose elimination of 6%, corresponding to a Q10 of 1.98 (SEM 0.12) with an energy of activation of 48 kJ/mol (SEM 4.7). Oxygen uptake was linearly related to galactose elimination (1.75 mol for 1 mole change in galactose elimination). These results indicate that circulatory changes are unimportant within physiological temperature changes. It is concluded that temperature effects on galactose elimination are too small to warrant a correction when used as a clinical test of quantitative liver function.

Adenosine Diphosphate↗
PubMed1986

The age dependency of the creatinine-related concentration of ribonucleosides in human urine.

We investigated the urinary excretion of ribonucleosides and an unidentified substance in 345 healthy probands from the age of a few weeks to 40 years. The concentration of ribonucleosides, related to the corresponding concentration of creatinine, decreases until nearly 20 years and remains constant between 20 and 40 years. The polynomial functions describing this dependency are presented. The biological significance of our findings is briefly discussed.

Adolescent↗
PubMed1985

Nuclear polymorphism in osteosarcomas as a prognostic factor for the effect of chemotherapy. A quantitative study.

A current strategy for osteosarcoma treatment is neo-adjuvant chemotherapy prior to the resection of the tumour. It appears that some tumours respond very well to the cytostatic therapy, while others show little or no effect. It is desirable to be able predict the response of the tumour before starting chemotherapy. 16 biopsy specimens from patients with osteosarcoma who had been treated according to the protocol of the study COSS-80 and COSS-82 were examined. 100 tumour cells from each biopsy have been measured by an electronic interactive image analysis system (IBAS II; Kontron/ZEISS). After completion of chemotherapy en bloc resection of the tumour was performed. The entire surgical specimen was completely examined at two levels by means of undecalcified sections, and assigned a grade for the effect of chemotherapy analogous to the grading of Salzer-Kuntschik et al. (1983). The quantitative analysis of tumour cell nuclei revealed two different patterns of nuclear sizes, which were correlated significantly with the chemotherapy response (P less than 0.002). Tumour cell nuclei of well responders were significantly larger and showed a greater variance in size (mean value 66 + 41 micron 2), than those of poor responders (mean value 38 + 18 micron 2). We conclude from our results that quantitative analysis and classification of nuclear size of osteosarcoma cells may be useful for predicting chemotherapy response in patients with osteosarcoma.

Adolescent↗
PubMed1985

[Comparison of x-ray and histological findings in osteosarcomas following preoperative chemotherapy].

Since the introduction of pre-operative chemotherapy, osteosarcomas have shown a more favourable prognosis. Reaction of the tumour due to chemotherapy is judged pre-operative primarily by radiology (plain films, angiography, CT, scintigraphy). There is little evidence concerning the radiological appearances after pre-operative chemotherapy and morphological changes, particularly in respect of tumour regression. Specific radiological changes were therefore compared with pathological findings following chemotherapy and operation in 17 patients with osteosarcomas. Tumours were examined which showed radiological evidence of intra-and extra-osseous sclerosis or lysis and which still were classified as vital tumour tissue. Tumour planes were reconstructed from large histological sections of the operative specimen and compared with the radiological appearances. Sclerosis was found to be due to reactive new bone formation or to mineralisation of the osteosarcomatous tissue. Lysis correlated with persistent vital tumour, or in connective tissue. Nine out of ten cases, regarded as vital on radiological evidence, showed vital tumour cells on histological section. Lyses and scleroses were not reliable indications of the pre-operative state of the osteosarcoma following chemotherapy. On the other hand, combined qualitative radiological criteria for assessing tumour vitality, proved to be helpful.

Adolescent↗
PubMed1985

[Bone scintigraphy in assessing the success of chemotherapy in osteosarcoma].

During preoperative chemotherapy regional 99mTc-MDP clearance by tumor and healthy bone as well as tumor blood flow were determined in 13 patients with osteosarcoma. The results were compared to histologic regression grades. After good response (tumor vitality less than 10%) tumor blood flow normalized and regional 99mTc-MDP clearance decreased by 66% (range 56-82%). After poor response to chemotherapy (tumor vitality greater than 10%) tumor blood flow remained increased, whereas regional 99mTc-MDP clearance was unchanged or increased except in one patient. After 4-7 weeks of chemotherapy tumor viability was accurately assessed in 8 of 9 patients (89%) by means of regional 99mTc-MDP clearance. Tumor viability could be evaluated also by simple tumor/non-tumor ratios. A decrease of 99mTc-MDP clearance by more than 20% indicated an effective chemotherapy with a specificity of 80%. After 10-13 weeks of chemotherapy the specificity was improved including the results of tumor blood flow determination.

Adolescent↗
PubMed1984

Quantitative reticuloendothelial function of liver and spleen in man.

A method for separate determinations of liver and spleen reticuloendothelial function, using a small-size 99Tcm -antimony sulphide colloid and gamma camera technique, is described. Several methods for achieving blood-background correction are examined, and it is shown that, by a three-compartment model, the use of a specific blood pool tracer can be dispensed with. Hepatic and splenic uptake of the colloid can be described by first order kinetics, and can be calculated to an error less than 5%. In a reference material (n = 13), hepatic and splenic clearance was 262 ml/min (100-412) and 22 ml/min (0-62), respectively. In cirrhosis (n = 7), hepatic clearance was decreased and splenic clearance increased. The results indicate that this method, which is well suited for clinical studies and which is based on a reasonable physiologic model, in cirrhosis of the liver demonstrates a decreased hepatic reticuloendothelial function with (compensatory?) increase in that of the spleen.

Antimony↗
PubMed1984

Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study.

From December 1979 to August 1982 158 patients were registered for an adjuvant chemotherapy (CT) study COSS -80. To compare the effect of cisplatin (CPL) to that of the drug combination bleomycin, cyclophosphamide, and dactinomycin (BCD), patients were randomized to receive either drug(s) within a course of sequential multidrug CT including doxorubicin and high-dose methotrexate (HDMTX). Definite surgery was done 10-18 weeks after the start of CT. Patients were randomized a second time to receive or not to receive fibroblast interferon in addition to CT beginning at week 16. At a median observation time of 19.5 months (range, 4-34 months), 116 (73%) of 158 patients were continuously disease-free (CDF). After exclusion of 42 patients because of some deviation in history and/or management, 86 (74%) of 116 patients actually were CDF with a 30-month calculated CDF-rate of 68%. There was no difference in CDF rates in the patients receiving BCD versus CPL or receiving interferon versus no interferon. Whereas, in comparison to the previous study COSS -77, the over-all increase in CDF rate does not reach statistical significance, it does, however, for the younger (less than or equal to 12 years) and for male patients, which is assumed to be the effect of increasing the methotrexate dose from 6 to 12 g/m2 in the COSS -80 study.

Adolescent↗
PubMed1983

Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake.

Some alcoholics have a regular daily alcohol consumption of more than 100 g. In preliminary observations we had the impression that the claimed alcohol intake in such 'heavy drinkers' was higher than could be accounted for by the ethanol elimination rate as measured routinely at 10 mmol/l (0.5 g/l). We therefore measured the ethanol elimination rate at very high blood ethanol concentrations of 40-80 mmol/l (2-4 g/l) found in eight alcoholics following heavy alcohol intake by measuring the falling blood ethanol concentrations until being less than 1 mmol/l. The elimination rate, on average 83 mumol/min per 1 blood, was about 49% higher than the elimination rate measured at 10 mmol/l in the same subject, being on average 58 mumol/min per 1/blood (paired t-test, P less than 0.05). The elimination rate following the high initial ethanol concentrations remained high until the concentration was below 5 mmol/l. Calculations of elimination rates are based on a number of assumptions concerning the physiologic and metabolic conditions. We examined specifically if the concentration-time curves could be adequately described by assuming metabolism according to a Michaelis-Menten pathway with a low Km value (simulating alcoholdehydrogenase with Km 0.2 mmol/l) or by assuming metabolism by two pathways with an alternative high-Km pathway with Km about 10 mmol/l. It was not necessary, in the statistical analysis, to include an alternative high-Km pathway. On the other hand, the data does give room for up to 50% elimination via such alternative pathways. The elimination rate at the high concentrations corresponded roughly to the claimed daily alcohol intake; furthermore the measured elimination rate at the lower concentrations were similar to values in non-alcoholics.

Alcohol Drinking↗
PubMed1983

Multivariate analysis of urinary RNA catabolites in malignancies: cross-sectional and longitudinal studies.

Urinary RNA catabolites, especially modified nucleosides and nucleobases, have turned out to represent valuable new criteria for diagnosis and follow-up of malignancies. Here we show for the first time that multivariate analysis of urinary RNA catabolites can distinguish between tumor carriers and controls who, if examined by univariate procedures, would remain undifferentiated. Two such models have been demonstrated. We hope that a continuation of this work will support primary clinical diagnostic procedures, the control of therapy effects, and the long-term follow-up of patients, which should be regarded as special medical applications of the general principles of molecular biology.

Analysis of Variance↗
PubMed1983

Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.

Adult↗
PubMed1983

Toxicity associated with combination chemotherapy for osteosarcoma: a report of the cooperative osteosarcoma study (COSS 80).

The treatment-associated toxicity in 189 patients entered in the COSS-80 Study was analyzed. The sequential use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and cis-platinum may be additive or synergistic in causing renal toxicity. However, evaluation of the 48-h serum methotrexate level and the incidence of elevated serum creatinine levels throughout treatment failed to indicate prolonged methotrexate elimination or severe kidney damage from this regimen where an interval of 3 weeks between cis-platinum administration and the next course of HDMTX was mandatory. The treatment-related mortality was 3.2% (6 out of 189 patients). Three patients died of septicemia during chemotherapy-induced bone-marrow depression following treatment with adriamycin or the combination of bleomycin, cyclophosphamide, and dactinomycin (BCD). Three deaths occurred following the use of high-dose methotrexate with citrovorum factor rescue. Two of these deaths were associated with delayed excretion of methotrexate. The toxicity is within the range reported in the literature.

Acute Kidney Injury↗
PubMed1983

General and regional haemodynamic effects of intravenous ergotamine in man.

The effect of intravenous ergotamine on general (blood pressure and cardiac output) and regional (splanchnic, renal and muscular) haemodynamics was studied immediately and 3 h after administration in seven male volunteers. Also plasma catecholamines were determined. An increase in blood pressure with a peak just after administration was observed. The cardiac output was unchanged and the pressor effect of ergotamine was due to an increase in total peripheral resistance. Plasma noradrenaline decreased 65% at the peak of the pressor effect whereas plasma adrenaline was unchanged. Hepatic blood flow decreased 34% just after ergotamine administration and was normal after 3 h. Renal blood flow decreased by 29 and 19%. Calf blood flow was unchanged. These results suggest that different vascular beds in man react differently to ergotamine.

Adult↗
PubMed1983

Splanchnic galactose uptake in patients with cirrhosis following single injection.

The galactose elimination capacity is used as a quantitative liver function test and is supposed to express the functioning liver cell mass. Clinical observations indicate, however, that the galactose elimination capacity overestimates functioning liver cell mass, and we therefore compare hepatic (splanchnic) and extrahepatic, extrarenal galactose elimination after a single injection of galactose in 23 patients with reduced liver function. The galactose elimination capacity was consistently greater than the hepatic (splanchnic) galactose elimination rate, estimated during liver vein catheterization. The difference was on the average 0.68 mmol min-1 (SD +/- 0.19, P less than 0.001) or about 40% of the galactose elimination capacity. If this difference, partly or fully, is due to extrahepatic extrarenal elimination, the clinical test for galactose elimination needs a correction (of the order of magnitude of 0.7 mmol min-1) to serve as an absolute measure of the hepatic functional capacity, but since the hepatic uptake rate may be underestimated following a single injection, the correction may be smaller.

Catheterization↗
PubMed1983

Splanchnic galactose uptake in patients with cirrhosis during continuous infusion.

The galactose elimination capacity (GEC) is considered a test of functional liver cell mass. The main uncertainties of the method are the effects of extrahepatic elimination and of uneven distribution in the body on the calculated maximal elimination rate of galactose. This has been evaluated by hepatic and renal venous catheterization during continuous infusion of galactose at two arterial concentration levels (mean 6.0 and 8.7 mmol l-1) in 10 patients with reduced liver function. Hepatic and renal blood flow were measured by constant infusions of Indocyanine Green and 131I Hippuran. Hepatic galactose elimination rate was identical (mean 1.36 and 1.32 mmol min-1, P greater than 0.4) at the two arterial concentration levels studied, indicating that hepatic galactose elimination rate was maximal (Vmax). The total body galactose elimination rate, calculated as amount infused during steady state, was 1.4 times greater than the hepatic elimination rate, calculated as arterio-hepatic venous concentration difference times hepatic blood flow. Within the experimental error, the extrahepatic (i.e. total minus hepatic) galactose elimination could be accounted for by renal elimination. The steady state studies show that the galactose elimination capacity, estimated from single injection, overestimates the hepatic Vmax by about 25%. The reason for this is probably mainly distribution phenomena and insufficient correction for urinary loss, but extrahepatic metabolism of galactose cannot be excluded.

Catheterization↗