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The effect of dopamine on hemodynamics (CO, AoPm, TPR, SV, SW, CVP, PAPm, PAEDP), microcirculation (MBF, PS-product) and renal function (VU, CKI, CNa, CK, Cosm, TcH2O) was studied in 8 patients with hypnotic drug poisoning. With increasing doses of dopamine, cardiac output and heart rate increased and the peripheral resistance decreased. An augmentation of stroke volume and left ventricular stroke work was observed in the low dose range only (200--400 mug/min). With increasing doses, central venous pressure as well as mean pulmonary artery pressure and enddiastolic pulmonary artery pressure decreased. No vasoconstriction was found in muscle tissue vessels even with large doses of dopamine. This is explained by the vasoplegic properties of hypnotic drugs. In circulatory shock associated with hypnotic drug poisoning, dopamine develops only minor pressure effects in contrast to its action in circulatory shock of cardiogenic or septic shock origin. High doses of dopamine result in a significant increase in heart rate, without concomitant increase in stroke volume and blood pressure. Therefore the dosage of dopamine should not exceed 400 mug/min in these cases. A combination with small doses of norepinephrine (10--20 mug/min) seems to be more effective. Renal function tests showed variable expansion of urine volume, glomerular filtration rate, and clearances of sodium, potassium and osmotic substances. Therapy with dopamine might increase the renal elimination rate of hypnotic drugs.

In a prospective study salivary magnesium was measured by atomic absorption spectrophotometry in 168 patients on chronic digoxin therapy. Magnesium concentration in saliva was correlated with clinical data and plasma digoxin levels. A significant elevation in salivary magnesium concentration was caused by digoxin therapy (0.58 +/- 0.39 mmol/l, n = 93) in comparison to patients with no digitalis treatment (0.17 +/- 0.07 mmol/l, n = 35). Magnesium concentrations in saliva were significantly higher in toxic patients (1.1 +/- 0.68 mmol/l, n = 32) than in nontoxic patients. Possibly toxic patients showed a magnesium level of saliva of 0.63 +/- 0.39 mmol/l (n = 40). In 89% of the intoxicated patients salivary magnesium concentrations were higher than 1.0 mmol/l. The overlap of magnesium between toxic and nontoxic patients was less as compared to calcium and potassium concentrations in saliva. No changes were noted in serum magnesium levels. Magnesium concentration in saliva was influenced by chronic digoxin therapy only. No significant increase of magnesium in saliva was observed within 24 h after i.v. injection of 1.0 mg digoxin in four healthy volunteers. It is concluded that salivary magnesium concentration is a valid method for monitoring digoxin therapy in addition to plasma digoxin levels.

The activities of serum cholinesterases were determined in parallel with acetyl-, butyryl- and propionyl-thiocholiniodide in healthy persons and patients with acute and chronic hepatitis, cirrhosis of the liver, fatty liver, cholestasis, intoxication and malignant tumors. The following normal values were obtained: See Article. The correlations between the various methods, especially between butyryl- and propionylthiocholiniodide are statistically significant. Compared to healthy persons, the activity of serum-cholinesterases, determined with the three substrates, decreased significantly in patients with acute and chronic hepatitis, cirrhosis of the liver, intoxication and malignant tumors. A change of specificity of serum-cholinesterases towards acetyl-, butyryl- and propionylthiocholiniodide in normal persons and patients with endogenous or exogenous coma of the liver was not observed. In all cases a parallel decrease of activity in sera was determined.

Wilson's disease in a young woman presenting with an acute course is described. The clinical manifestations were fulminant hepatic failure associated with marked intravascular hemolysis. Immediate D-penicillamine and high-dose steroid therapy did not influence the course of the disease. Necropsy revealed an increased hepatic copper content and cirrhosis with extensive necrosis of the liver.

This study demonstrates the changes of concentration and elimination of calcium, phosphate and zinc, as well as alteration of serum alkaline phosphatase and acid phosphatase especially in patients with severe brain injuries in connection with bone fractures. Because the study has not been completed, the presently acquired results should only demonstrate possible development of the examined parameters. To find out the pathogenesis of overgrowing callus in brain-injured patients, further examinations are being carried out to find the histochemical activities of alkaline and acid phosphatase, lactate dehydrogenase, adenosine triphosphatase and acetylcholine esterase.

Two methods based on different chemical and physical principles for the determination of selenium in serum are elaborated, evaluated and compared--the hydride atomic absorption (AAS) technique and the carbon furnace technique. For the hydride AAS technique a wet destruction method is described. The sensitivity of the method is 10 micrograms Se/1. The carbon furnace technique makes use of the fact that selenium forms refractory selenides when nickel compounds are added. The sensitivity of the carbon furnace technique is 11 micrograms Se/1. The determination of selenium in serum by the hydride AAS and carbon furnace technique correlates satisfactorily (correlation coefficient 0.94; mean value for the hydride AAS 69.1 micrograms Se/1; mean value for the carbon furnace 67.4 micrograms Se/1) indicating that with the carbon furnace technique total selenium (inorganic and organic) is determined. A reference range was established with 99 persons (42 men and 57 women) which show an average selenium content in serum of 80.55 (SD 13.78) micrograms Se/1 [1.02 (0.17) mumol Se/1].

The selenium content of food consumed in the Federal Republic of Germany (FRG) was determined for the estimation of the dietary selenium intake of West German adults. The daily dietary selenium intake of men is 47 micrograms (micrograms) and that of women 38 micrograms, corresponding to 0.67 microgram/kg body weight per day for both men and women. Animal protein is the main source of dietary selenium, accounting for 65.5% of the total selenium intake. Pork contributes 25.1% to the total Se intake, reflecting the current consumption and the selenium supplementation of feedstock rather than the availability of selenium from natural dietary sources. The selenium intake of adults in West Germany is only slightly higher than in New Zealand, Finland, and Italy, nearly equal to that in Belgium and France, and distinctly lower than in Great Britain, the USA, Canada, and Japan.

A fully mechanized immunonephelometric method is described for the rapid and specific determination of apolipoprotein A-II in serum. The method utilizes commercially available sheep antiserum against human apolipoprotein A-II. Nephelometry was performed with the Behring Nephelometer Analyzer (BNA). A single determination can be performed in 12 minutes, requiring 10 microliters sample volume. The measuring range is about 0.08 to 1.25 g/l apolipoprotein A-II. Precision is characterized by intra-assay coefficients of variation of 3.37%, 3.93% and 4.49% for apolipoprotein A-II concentrations of 1.22 g/l, 0.376 g/l and 0.185 g/l, and inter-assay coefficients of variation of 4.27% for an apolipoprotein A-II concentration of 0.404 g/l, respectively. Accuracy of the method is shown by the close correlation of results with those from radial immunodiffusion (r = 0.913, y = 1.091 x -0.033, n = 75).

In skeletal muscle isoenzymes of CK were determined by immunprecipitation and chromatography. The activity of CK-MB was between 17 and 47 U/g muscle, corresponding to a quota between 2,1 and 4,2% of the total activity. In sera of patients with muscular dystrophy, polymyositis, hypothyroidism, after arterial embolism, epilepsy, hyperventilation, operations and polytrauma with and without injury to the thorax isoenzymes were measure by immune precipitation- and immune inhibition-test. The percentage of CK-MB in all sera was less than 6% of the total CK-activity (range: 0 to 6%). Only patients in the first day after neurosurgical operations showed a quota till to 6.5% CK-MB. In serum of patients after polytrauma without injury to the thorax the percentage of CK-MB ranged from 0-5.7% while after polytrauma with injury to the thorax and a reasonable suspicion of a damage to the myocardium this quota was between 5.1 and 23.6% of the total activity. CK-BB activity was not detectable in any cases. Therefore a disease or damage of the skeletal muscle is more probable, if the percentage of CK-MB in less than 6%, because in sera of patients with myocardial infarction in the first 48 h after beginning of the symptoms this quota of CK-MB in the most cases in more than 6%.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.

A human hepatoma cell line, associated with thorotrast exposure, from an hepatitis B marker-negative patient was established as a permanent cell line (Mz-Hep-1) in tissue culture. Histology of the primary tumor, as well as phase contrast, transmission and scanning electron microscopy of the cultured cells showed typical characteristics of liver cells. Mz-Hep-1 cells secreted complement components (C2, C3, C4), carcinoembryonic antigen, lactate dehydrogenase, chymotrypsin, haptoglobin and retinol-binding protein and expressed HLA-, transferrin-, blood group B-related determinants and complement component C5 and carcinoembryonic antigen on their cell surface. Mz-Hep-1 cells represent the first human hepatoma cell line, which is strongly associated with a carcinogen.

A deficiency of selenium is suspected to be involved in the pathogenesis of congestive cardiomyopathy. Therefore the serum selenium content of 20 patients with proven congestive cardiomyopathy was measured and compared to that of a healthy control group. The serum selenium content of the patients with cardiomyopathy was found to be different from that of the healthy control group. The mean value of selenium in serum for the control group was 80.1 micrograms Se/1 (SD +/- 13.2) within a range of 53 and 117 micrograms Se/1. From the 20 patients with congestive cardiomyopathy six patients showed selenium concentrations in the normal value range of the control group; in the serum of 14 patients a distinct lower selenium content was found (mean value 47.8 micrograms Se/1 (SD +/- 16.2)) within a range of 23 and 70 micrograms Se/1. A positive correlation was found between serum selenium content and the left ventricular ejection fraction. Our results suggest that a deficiency of selenium may be present in a number of patients with congestive cardiomyopathy.

Three human cell lines from adenocarcinomas of the extrahepatic biliary tract were established in permanent tissue culture. Mz-ChA-1 and Mz-ChA-2 were cultured from mechanically dissociated gallbladder adenocarcinoma metastases and SK-ChA-1 was grown from malignant ascites of a patient with primary adenocarcinoma of the extrahepatic biliary tree. Cell doubling times in tissue culture are 3-4 days for Mz-ChA-1 and approximately 2 days for Mz-ChA-2 and SK-ChA-1. All three tumour cell lines were successfully transplanted to nude mice, inducing progressive tumour growth. Histologically, nude mouse tumours resembled the original adenocarcinomas. In vitro formation of gland-like structures were regularly seen in Mz-ChA-1 and Mz-ChA-2 but only occasionally in SK-ChA-1. All three cell lines formed contacts through interdigitating processes with desmosomes and junctional complexes. On scanning electron microscopy, an abundance of microvilli was seen at the cell surfaces. Chromosome analyses of all three tumour cell lines showed a wide range of numerical abnormalities and presence of marker chromosomes. Mz-ChA-1 appears to be highly differentiated with cells producing mucus. Mz-ChA-2 synthesizes components of complement C2, C3 and C5, while Mz-ChA-1 and SK-ChA-1 produce only C3 in detectable quantities. In addition, Mz-ChA-2 supernatants are positive for ferritin and alpha 1-fetoprotein, but not CEA; while Mz-ChA-1 and SK-ChA-1 produce only CEA. Supernatants of all three cell lines are positive for N-acetyl neuraminic acid (NANA), phosphohexoisomerase (PHI) and LDH, and negative for alpha 2-macroglobulin, alpha 1-anti-trypsin, gamma-GT, AP, coeruloplasmin, haptoglobin and albumin. A high cloning efficiency renders these new tumour cell lines suitable for continued studies on clonal heterogeneity in malignant tumours. The establishment of these cell lines in tissue culture facilitates further studies on the biology of upper gastrointestinal tract cancer in man.

A new method for the determination of creatine kinase-MB activity in the serum is presented. The principle of this method is the direct measurement of the activity of creatine kinase M subunits by inhibiting antibodies. The total test procedure takes 15 min. In the sera of all the 83 patients tested, who have clinically proven myocard infarction, creatine kinase-MB activity can be measured between the 6th and 28th hour after infarction. At the time of maximum total creatine kinase activity the percentage of creatine kinase-MB activity is between 6 and 17%, the mean value being 8%. In cases of emergency this method can be used for the differential diagnosis of elevated total creatine kinase activities of unknown origin.

Serum selenium concentration was determined in 49 patients with acute myocardial infarction within 4 hours after the beginning of the symptoms. The mean serum selenium concentration of the patients was significantly lower than that of healthy controls (55 +/- 15 micrograms/l vs. 78 +/- 11 micrograms/l). Among the 49 patients with acute myocardial infarction 20 (41%) had serum selenium concentration below the 95% percentile of the healthy control group. It is concluded that the low serum selenium concentration was present in these patients before the acute event and was not a consequence of the myocardial infarction. No relationship was found in this study between the serum selenium concentration and the severity of myocardial infarction if the number of coronary vessels occluded is taken as the criterion of severity. Serum selenium concentration was similar in patients with 1 or more coronary vessels occluded. Patients with anterior or posterior myocardial infarction had similar serum selenium concentrations. A positive correlation was observed between serum selenium concentration and total serum creatine kinase (CK) activity and serum myoglobin (MB). The serum selenium concentration correlated negatively with the ratio CK-MB/total CK activity, which can be interpreted as minor injury of mitochondria during infarction in patients with normal serum selenium concentration.

The fibrinolytic efficacy and systemic effects on coagulation variables of intracoronary administration of an acylated streptokinase-plasminogen complex (BRL 26921) were assessed in 23 patients with an acute transmural myocardial infarction. The infarct vessel was totally occluded in 22 patients and subtotally stenosed in 1 patient. Reperfusion was achieved in a total of 17 patients (74%), in 2 patients with the use of a guide wire. Reperfusion time in those patients treated with BRL 26921 alone amounted to 42 +/- 37 minutes. Reocclusion occurred in two patients subsequently. Four patients died; in two of these, intracoronary thrombolysis was unsuccessful. Reptilase time increased from 13 +/- 3 to 49 +/- 31 seconds (p less than 0.001), fibrinogen levels decreased from 280 +/- 65 to 126 +/- 76 mg% (p less than 0.001). Factor V decreased from 96 +/- 11 to 53 +/- 26% (p less than 0.001), and factor VIII from 99 +/- 1 to 55 +/- 36% (p less than 0.001). Peripheral hyperplasminemia, defined as a reduction of fibrinogen (less than 100 mg%) with a reduction of factor V and VIII (less than 75%) simultaneously occurred in eight patients. Six (75%) of these 8 patients demonstrated reperfusion, whereas 9 (64%) of 14 patients without peripheral hyperplasminemia were also successfully reperfused. Bleeding complications occurred in two patients who demonstrated hyperplasminemia. Thus, effective intracoronary thrombolysis could be achieved with only minor effects on peripheral coagulation variables in the majority of patients.

Patients on chronic hemodialysis may suffer from a latent protein deficiency, and therapy with essential amino acids has been recommended. In a double blind cross-over study, 13 hemodialysis patients received orally 15.7 g of essential amino acids daily over a 3-month period. Patients were on a liberal diet, containing 1 g of protein per kilogram of body weight per day. Hemodialysis was adequate. Therapy resulted in an increase in urea, uric acid, C3 c complement factor and a fall in C4. Lysine levels increased and phenylalanine fell. Malnutrition could not account for the observed metabolic changes, which are more likely due to uremic metabolic disturbances. A liberal diet of 1 g of protein per kilogram of body weight appears sufficient for patients on hemodialysis. Treatment with essential amino acids offers no advantage.

Analysis of human serum aldolase isoenzymes A, B and C activities was performed by means of a recently developed immunochemical assay. Isoenzyme patterns were established in 130 healthy subjects selected from a normal range research program. Total aldolase activity ranged from 0.8, 1.6, 2.5 U/L, Ald A from 0.6, 1.2, 1.9 U/L, Ald B 0.0, 0.2, 0.7 U/L, Ald C 0.0, 0.1, 0.4 U/L expressed as chi plus or minus 2 s range. Comparing the histograms of total aldolase activity in patients with acute hepatitis and normal controls, an almost identical frequency distribution in both groups was observed. However, histograms of aldolase isoenzyme B values of these groups were practically completely separated. Thus in contrast with total aldolase activity, the determination of aldolase isoenzyme B activity is a useful criterion in the diagnosis of acute hepatitis.

Antithrombin III (AT III) activity was determined with two different new chromogenic substances--Chromozym-TH (Tos-Gly-Arg-p-nitroanilide; Boehringer Mannheim) and alpha-N-carbobenzyl-oxy-L-lysine-thiobenzyl ester (Du Pont)--with both a discrete (aca) and a centrifugal analyzer (COBAS BIO). The correlation between the Chromozym-TH/centrifugal analyzer and Du Pont ester/aca methods was good (r = 0.9890). Precision within and between runs was similar to that for typical enzymic determinations. AT III in plasma of 226 healthy men and women ranged from 76.6 to 141.1% (100% = "normal"). We found no significant differences ascribable to oral contraceptives. AT III activity was decreased in 27% of patients with acute thromboembolic diseases (n = 62), in 48% of patients the first day after abdominal operations without complications (n = 78), and in 100% of patients with reversible or irreversible shock (n = 58). In patients receiving continuous therapy with heparin (1500 USP units/h) we saw no decrease in AT III within 96 h of beginning treatment. Plasma from 14 of 16 patients with disseminated intravascular coagulopathy showed a decrease in AT III of from 17 to 51% of normal before and during heparin therapy. We then treated all 16 patients with AT III concentrate. During such treatment, AT III in plasma must be monitored over short intervals to assure that sufficiently high proportions of AT III (greater than 70% of normal) are reached.

Streptokinase was infused for 103 +/- 25 hrs. in 27 patients (6 with deep vein thrombosis of the leg, 7 with thrombosis of Vv. axillaris and subclavia, 9 with acute massive pulmonary embolism, 3 with chronic artery occlusion, 2 with thrombosis of the retinal vein). Blood coagulation studies were performed repeatedly. Anticoagulation (prolongation of thrombin time to 1 1/2-2 1/2 of normal) could be achieved without additional heparin by reduction of streptokinase to doses as low as 20 000 U/h. Reptilase time correlated significantly with thrombin times. Following 24 hrs. of infusion, PTT was less than 50 sec. and Quick test less than 50% of normal in most instances. No correlation was found between PTT or Quick test and factor II, V, VI, X activities during streptokinase infusion. Bleeding was observed in 18 patients. The infusion was stopped because of bleeding in 3 cases. None of the coagulation tests performed in this study correlated with the incidence of bleeding. Hemoglobin concentration decreased 2,6 +/- 1,6 gr% and this decrease could no be explained by blood lesses.

Isoelectric focusing (IEF) of apolipoproteins is an important procedure for the isolation of apolipoprotein isoforms. In this paper we describe the use of agarose/urea as a focusing medium for IEF of apolipoproteins. This technique, which offers several advantages over the traditional polyacrylamide gel focusing, yields a further microheterogeneity of the known isoforms of apolipoproteins A-I and E. In addition, by subsequent immunoprecipitation, both specificity and sensitivity are enhanced. Using a monospecific antiserum against Apo A-I, a new minor isoform was detected at the basic end of the Apo A-I spectrum (pI 6.02) which has not yet been observed in normal plasma samples. Another advantage of this technique in combination with immunoprecipitation is the specific detection of Apo E phenotypes which is essential for the diagnosis of hyperlipoproteinemia type III.

In 15 ambulatory patients with renal insufficiency (creatinine clearance, 9.9 +/- 3.0 ml/min) the effect of oral supplementation with alpha-ketoacids has been compared with that of placebo. The protein intake amounted to 0.55 g protein per kilogram body weight of high biological value, as estimated by dietary recordings. After a control period of 3 months the patients received, in a double-blind study, 1.05 g alpha-ketoacids/10 kg body weight per day or a placebo for 6 weeks with a subsequent cross-over. Fasting blood samples were analyzed at 3-week intervals for routine laboratory parameters and 17 proteins. Anthropometric and clinical data have been recorded every 3 weeks. While therapy with alpha-ketoacids diminished PO4 levels (P less than 0.05), no other significant effect could be demonstrated. No signs of protein deficiency existed either before or during alpha-ketoacid therapy. Therefore, supplementation with alpha-ketoacids appears to be superfluous in patients with renal insufficiency maintained on a 40-g protein diet.

We measured Se, Zn, Fe, Cu, Mg, and K in blood and heart tissue of patients with coronary heart disease. Such patients have subnormal selenium concentrations in serum, whole blood, and (calculated per gram of hemoglobin) erythrocytes. Concentrations of zinc and copper in serum were also subnormal in these patients. Heart tissue collected from these patients during bypass surgery was analyzed for Se, Zn, Fe, Cu, Mg, and K; results are expressed in terms of wet weight and in relation to nitrogen and phosphorus content. Concentrations of these elements in blood are correlated with those in heart tissue. Selenium concentrations in serum correlated positively with those in tissue but not with those in erythrocytes. We found no association between concentrations of zinc, iron, copper, magnesium, and potassium in serum and the corresponding concentrations in heart tissue. There was a moderately positive correlation between the concentration of ferritin in serum and that of iron in tissue. We conclude that the turnover rate for selenium in tissue is similar to that in serum but greater than that for erythrocyte selenium. The concentrations of these six elements in heart tissue are partly correlated with the ejection fraction of the left ventricle.