[Atrial natriuretic factor levels and pressure in the pulmonary circulation before and after coronary dilatation]. / ANF-Konzentrationen und Drücke im kleinen Kreislauf unter Belastung vor und nach Koronardilatation.

According to several reports of close correlations between pulmonary artery pressure and ANF plasma levels it would be convenient to replace invasive pressure monitoring by ANF determination. Mean pulmonary artery and right atrial pressures and pulmonary artery as well as peripheral venous ANF plasma concentrations were measured in 24 patients before and after coronary angioplasty (PTCA) continuously at rest and during exercise: At rest, both pressure and ANF-values remained unchanged before and after PTCA. At exercise, there was a decrease of mean pulmonary artery pressure (from 41.3 +/- 8.6 to 31.5 +/- 7.4 mmHg, p less than 0.001), mean right atrial pressure (from 11.9 +/- 3.0 to 9.0 +/- 2.3 mmHg, p less than 0.001), pulmonary artery (282.5 +/- 191.0 to 207.3 +/- 157.2 pg/ml, p less than 0.05) and peripheral venous (112.7 +/- 48.0 to 97.1 +/- 53.2 pg/ml, n.s.) ANF concentration after PTCA. We found no correlation between PTCA-induced changes of right arterial pressures and ANF concentrations, while changes of pulmonary artery pressures were significantly correlated to changes of peripheral venous (r = 0.79, p less than 0.001) as well as pulmonary artery (r = 0.59, p less than 0.01) ANF concentrations at exercise. In 6 of the 24 patients, however there was an inverse relationship between changes of pulmonary artery pressures and ANF concentrations. - Our data demonstrate a significant correlation between changes of ANF plasma level and pulmonary artery pressure values at exercise after PTCA. In the individual case however invasive pressure monitoring cannot be replaced by determination of ANF plasma levels.

DNA in human glioblastomas. A flow-fluorescence cytometrical examination of 96 tumors.

The Flow-Fluorescence Cytometric Method (FCM) was applied to investigate the DNA content and the ploidy outlines of each of 96 glioblastomas. No specific DNA pattern was detected, possibly because of the tangle morphology of these variable tumors. Due to their capricious growth the DNA distribution proved to fluctuate greatly. Thus, the series, arranged according to increased PI (proliferation index) values, exhibited a wide spread within a total range from 7.1-97.15% (mean 39.3%) PI. A threefold subdivision of main types (I-III) appears to be of practical use for clinical prognostic assessment: "diploid" tumors with a PI range up to 10% (N = 7) are followed by "abnormal" chiefly tetra- and hyper-tetraploid tumors up to PI values about 30% (N = 21). The third category includes cases showing excessive "aneuploidy" combined more and more with polyploidy and valid stemlines, up to the PI maximum of about 97 rel.% (N = 68). Thus, in 89 tumors clear pathological changes of DNA content can be decoded; of these 68 (76.4%) express a considerable aneuploidy and polyploidy respectively.

DNA in chordomas of the clivus Blumenbachi.

Chordomas of the clivus are frequently denoted as malignant, mainly because of their propensity to recur, their crucial location and the fatal clinical course. Although microscopical examination commonly reveals pleomorphism, particularly of cells and nuclei, the histological assessment of malignancy is not always appropriate. The measurement of DNA could provide important information for a classification of their biological behavior (grading). Our examination of a chondroid chordoma revealed a typical diploid DNA curve within a "benign" 4C range concordant to the favorable course of this variant. Our second examination of a "typical" chordoma showed a wide pleomorphism of cell nuclei and moderate proliferation activity within a "low grade" scale. This pointed to a coming (fatal) recurrence 3.5 years after the first surgery. The third chordoma we examined presented an extraordinary 4C aneuploidy with hypertetraploid subpopulations and an increased number of bi- or poly-nucleated tumor cells with prominent nucleoli and some more mitotic figures. In 5 recurrences the DNA pattern remained principally unchanged.

Flow-cytophotometry of nuclear DNA in biopsies of 45 human gliomas and after primary culture in vitro.

DNA distribution in biopsies and cell cultures of human gliomas was examined by flow-fluorescence-cytometry using ethidium bromide staining. Glioblastomas (n = 25) showed "polyploid", "marked tetraploid", or "hypertetraploid" aneuploid karyograms, comparable to subtypes previously proposed by Japanese authors. "Diploid-hyperdiploid" DNA patterns were manifest in 3 cases plus 1 sarcoma--glioblastoma, containing abundant rapidly growing mesenchymal cells. Most tumors showed S-phase increment. "Near-diploid" patterns could be a result of aggregated cells, and small 4 C peaks could be due to non-representative specimens (3 cases). During cultivation, the DNA distribution usually remained stable, but maxima occasionally shifted. Oligodendrogliomas (n = 11) and astrocytomas (n = 9) of low-grade showed low 4 c peaks. High-grade gliomas, however, showed abnormal DNA patterns. Thus, one case of an oligodendroglioma--I developed an abnormal "marked tetraploid" glioblastoma after a 3-year interval presenting its malignant transformation. DNA distribution can obviously vary during tumor evolution. However, it may well support the assessment of grading and more closely define the prognosis in gliomas.

Comparative analysis of myocardial enzyme activities of the energy-supplying metabolism in patients with dilative cardiomyopathies and valve diseases.

We determined representative enzyme activities of glycogenolysis (glycogen phosphorylase) glycolysis (d-glyceraldehyde-3-phosphate dehydrogenase, GAPDH), beta oxidation of free fatty acids (1-3-hydroxyacyl CoA dehydrogenase, HADH), citric acid cycle (citrate synthase, CS), lactate fermentation (lactate dehydrogenase LDH), and creatine phosphate metabolism (creatine kinase, CK) in left ventricular samples of 36 patients to investigate if the metabolic capacities of the energy-supplying pathways are differently affected in different heart diseases. There were 17 patients with mitral valve diseases (MVD), 8 patients with aortic valve diseases (AVD), and 11 patients who suffered from dilative cardiomyopathies (DCM). The main metabolic characteristic on the level of enzymatic organization in patients with DCM was an increased ratio of GAPDH/HADH activities and a decreased ratio of HADH/CS activities compared to the valve-diseased patients. This result indicates that the capacity of glucose oxidation is enhanced at the expense of fatty acid metabolism in patients with DCM. Furthermore, we determined significantly lower myocardial CK activities in this group of patients, most probably reflecting a diminished content of myofibrils. Citrate synthase activity was lowest in patients with AVD. Although we cannot rule out that the impaired left ventricular function is in part responsible for the shift of the capacities of the energy-supplying metabolism in patients with DCM, we favor the assumption that it is a specific feature of this myocardial disease.

[Rhabdomyolysis as a complication of chronic alcoholism. Observations in 19 cases]. / Rhabdomyolyse als Komplikation des chronischen Alkoholismus. Beobachtungen bei 19 Fällen.

In 19 chronic alcoholics with rhabdomyolysis the clinical picture demonstrated markedly different degrees of severity of myolysis. Muscle pain, muscle swellings and brown-coloured urine were rare. But symptoms of delirium, at times with cerebral seizures, were frequent at the onset. Renal failure of different degrees was common; five patients had to be dialysed. Two patients died in irreversible shock. Respiratory insufficiency and hypercalcaemia were other complications. Early recognition of the disease is important, because early treatment can prevent acute "myoglobinuric" renal failure.

The effect of chronic ethanol consumption on enzyme activities of the energy-supplying metabolism and the alcohol-aldehyde oxidizing system in rat hearts.

We investigated in rat hearts if chronic alcohol consumption causes an enzymatic adaption of the energy-supplying metabolism and/or of the alcohol-aldehyde metabolizing system. 16 rats were pair-fed with a liquid diet for 10 weeks. Ethanol was added to this diet to amount for 35% of calories in eight rats and was isocalorically replaced by saccharose in the control group. Selected enzyme activities of the glycolysis, the glycogenolysis, the beta-oxidation of fatty acids, the citric acid cycle and the alcohol-aldehyde oxidizing system were determined in the supernatants of the homogenized hearts. The intracellular redox state was assessed by measurement of the myocardial nicotinamide coenzymes. Enzyme activities of the alcohol-aldehyde metabolizing system did not alter after chronic alcohol intake. As we found that the capacity to oxidize acetaldehyde was much higher than the ability to oxidize ethanol we must question the role of acetaldehyde in inducing alcoholic cardiomyopathy. Chronic ethanol treatment significantly increased the activity of glyceraldehyde-3-phosphate dehydrogenase and decreased the activity of glycogen phosphorylase. The impairment of the hydroxyacylCoA dehydrogenase was not significant. The other measured enzyme activities did not alter, nor the intracellular redox state. The enzymatic adaption indicates an impaired glycogenolysis, an increased glycolysis, and probably a diminished beta-oxidation of fatty acids. We expect that the measurement of the responding enzyme activities in human endomyocardial biopsies should be a good tool to further classify cardiomyopathies according to biochemical criteria.

[Elevated serum myoglobin in renal failure (author's transl)]. / Erhöhtes Serum-Myoglobin bei Niereninsuffizienz.

In 44 patients with chronic renal failure of varied etiology serum immunoreactive myoglobin was measured and compared to values obtained in patients with normal renal function. Irrespective of the underlying disease a highly significant linear correlation was found between serum immunoreactive myoglobin and serum creatinine concentration. In patients with serum creatinine concentrations above 550 mu mol/1 (6.2 mg%) serum myoglobin was as a rule elevated above the range found in the controls with normal renal function. This was also true in dialysis patients. These result demonstrate that serum myoglobin may only be used with restrictions in the diagnosis of myocardial infarction in patients suffering from advanced chronic renal failure.

[Radioimmunoassay for human myoglobin: methodology and diagnostic significance in myocardial infarction (author's transl)]. / Radioimmunologische Bestimmung von Human-Myoglobin in der Diagnostik des akuten Myokardinfarkts.

A radioimmunoassay was developed to determine serum myoglobin (SMb). 50 healthy persons showed values between 0 and 90 ng/ml. Serial tests of 10 patients following acute myocardial infarction or during angina pectoris (AP) indicated that SMb reached pathological values before CK and CK-MB (average 250 +/- 95 ng/ml at the time of hospitalisation which corresponds to 3.3 +/- 1.4 h after beginning of angina pectoris). At hospitalisation the simultaneously determined CK was within normal limits and reached pathological values only 6.2 +/- 1.9 h after the onset of angina. Maximum of SMb was 506 +/- 194 ng/ml occurring 8.8 +/- 2.8 h after beginning of AP, maximum of CK was 905 +/- 475 mU/ml occurring 20.0 +/- 7.8 h after AP. CK-MB and CK differed only slightly in their time course. One patient with severe AP had pathologically increased SMb values whilst all other enzymes were completely normal. Methodical and clinical results are discussed.