Determination of renal clearance of neopterin by a pharmacokinetic approach.

Pharmacokinetic modelling was used to determine the glomerular filtration rate and tubular secretion of neopterin, a marker for cellular immune activation. The method involves parameter identification employing the transient venous plasma concentration profiles of marker substances. By combined i.v. injection of neopterin and inulin which is excreted exclusively via glomerular filtration, neopterin was shown to be excreted in addition to glomerular filtration, by tubular secretion: clearance of inulin, 112 (S.D. 2.2) ml/liter; clearance of neopterin, 499 (S.D. 79.7) ml/min. A pilot experiment using in addition p-amino hippuric acid suggests that neopterin and p-amino hippuric acid may employ the same carrier system for tubular secretion.

In vitro long-term perfusion of different materials for biliary endoprostheses.

An in vitro perfusion of Teflon, polyethylene, polyurethane, and Percuflex TM catheters with human bile was performed to estimate the incrustation rate of the different materials. Microscopic and chemical analyses revealed the highest incrustation rate on Teflon and the lowest on polyurethane (about four times lower than on Teflon). For each material the probable minimum value for the duration of patency of an endoprostheses of a 3-mm inner diameter was calculated.

Detection and evaluation of persisting stress-induced hormonal disturbances by a post stress provocation test in humans.

Eighteen healthy army officers were subjected after prolonged rest to exhaustive ergometric work for about 15 minutes. Before and afterwards blood was taken from the cannulated antecubital vein for determination of free and sulfoconjugated catecholamines, cortisol, glucose, and white blood cell count. One week later, the same procedure was repeated with the same subjects with the difference that the probands underwent about 2.5 hours of difficult mountain climbing and a subsequent rest of 1.5 hours before ergometry. The most important results were: 1) total and bound fractions of catecholamines showed some significant differences between the first and second ergometry due to the previous mountain climbing stress; 2) serum cortisol did not increase after the first ergometry but did so significantly after the second ergometry due to the previous stress; low cortisol is not always indicative of the absence of stress; 3) the absolute number of white blood cells increased in both situations, correlated significantly with the severity of the stress and the individual increases were more person than situation specific and; 4) blood glucose remained unaffected in both situations. We conclude that a previous stress experience can affect a second stress response and that such a post stress provocation test can uncover persistent hormonal alterations. This procedure may be useful for the evaluation of inaccessible stress situations from subsequent stress measures.

Assay of phagocyte activation by means of malondialdehyde and luminol-enhanced chemiluminescence during uneventful wound healing following trauma surgery.

The purpose of the study was the assessment of the acute inflammatory response in patients (N = 12) with comparable trauma severity and uneventful wound healing courses in the postsurgical period as a contribution to the search for objectifiable criteria in the monitoring of wound healing. Whole blood chemiluminescence (CL) on the one hand and the lipid peroxidation product malondialdehyde (MDA) on the other hand as tools for the detection of the respiratory burst activity of phagocytes were used as inflammation markers and were compared with the established marker PMN elastase. Blood samples were withdrawn daily from the day of surgery to the 14th postsurgical day. CL-parameters and PMN elastase increased postoperatively reflecting surgical trauma, while MDA remained within the normal range during the whole time of observation. A decrease of CL-activity in the postsurgical period correlated with decreasing PMN elastase levels (r = 0.52, P<0.0001) as well as with the tapering of local inflammation signs concerning the wound situs. MDA values neither correlated with PMN elastase nor with any CL-parameters. The results indicate that the measurement of the phagocytic activation by CL, used for the first time in traumatology to monitor wound healing, represents a promising marker for the assessment of the actual inflammatory status.

Relationship between generation and plasma concentration of anorganic phosphorus. In vivo studies on dialysis patients and in vitro studies on erythrocytes.

The plasma concentration of inorganic phosphorus (Pi) was determined before, during and after hemodialysis in 28 patients with chronic renal failure. Pi plasma concentration decreased rapidly when hemodialysis was started but did not fall below normal levels during continued dialysis. These changes of Pi concentration were fitted to a model of Pi kinetics in which Pi delivery to plasma is a nonlinear function of the extracellular Pi concentration. In separate in vitro studies, erythrocytes from six subjects with normal renal function and from 14 patients with chronic renal failure were incubated in homologous plasma with various amounts of Pi added. All other factors known to affect the Pi shift between intra- and extracellular fluid compartments (pH, calcium concentration) were kept constant. The relation between Pi concentration in plasma used for incubation and in red cells after 1h incubation suggested a mechanism in which a high plasma concentration results in movement of Pi into red cells where Pi is stored most probably in glucose esters. At low Pi plasma concentration Pi is delivered to plasma at a rate which cannot be explained solely by passive movement of intracellular Pi to plasma but requires additional generation from intracellular storage forms. The generation and delivery of Pi in patients and in their erythrocytes indicate a simple cell-mediated Pi homeostasis counter-acting abnormal fluctuations of plasma Pi.

[Serum lipase activity and evocation test after endoscopic retrograde cholangio-pancreatography (author's transl)]. / Serumlipaseaktivität und Serumlipaseevokationstest nach endoskopischer retrograder Cholangio-Pankreatikographie

Serum lipase activity, which is a more specific indicator of pancreatic damage than serum amylase activity, was determined in 51 patients before and immediately after endoscopic retrograde cholangio-pancreatography (ERCP) and 24 hours subsequently. An increase in serum lipase activity without clinical signs of acute pancreatitis was observed immediately after pancreatography in 20 cases. Increased serum lipase activity after 24 hours is largely observed in patients with parenchymography or those displaying increased values already in the fasting state before ERCP. This observation emphasizes the need for caution in the assessment of the indication for ERCP in patients with preexisting increased serum lipase activity in view of the very real risk of acute pancreatitis and the need to avoid parenchymography of the pancreas. According to our experience the addition of a broadspectrum antibiotic such as gentamycin to the contrast medium may, to a large extent, avoid the development of acute pancreatitis. Lipase evocation tests carried out 10 days after the ERCP showed negative results in patients with increased enzyme activity and parenchymography after pancreatography. Hence, it is concluded that ERCP causes symptomless reversible biochemical pancreatic changes, as opposed to irreversible pancreatic damage.

[Low molecule and middle molecule metabolites with haemodynamic activity in the ultrafiltrate from uraemic patients (author's transl)].

Substances causing blood pressure changes and myocardial damage in rats were first detected in the ultrafiltrate obtained from patients on long-term haemodialysis by means of size separation, high-voltage electrophoresis and thin-layer chromatography. Of the 100 to 140 fractions produced by Sephadex G 15 chromatography at least 3 raised the blood pressure when administered in doses of 2 to 10 mg/0.1 to 0.2 ml 0.9% NaCl, that is the high molecular fraction 18 to 23 and the low molecular fractions 71 to 72 and 73 to 74. The fractions 96 to 98 and 97 to 106 showed high toxicity. Less than 1 mg/0.1 to 0.2 ccm 0.9% NaCl produced cardiac arrest. The fractions 35 to 55, which originate from the middle molecules and are retained in regularly uraemia, contain substances which caused a reduction in blood pressure at low dosage and cardiotoxic effects at a dosage of more than 10 mg. Thin-layer chromatography indicates that the substances most probably consist of peptides whose structure contains the amino acids leucine, isoleucine, valine, glutamic acid, aspartic acid, alanine and cystine.

[Evidence of type-specific microheterogeneity of thyroxine-binding globulin by isoelectric focusing (author's transl)]. / Nachweis einer typenspezifischen Mikroheterogenität des humanen Thyroxin-bindenden Globulins durch isoelektrische Fokussierung.

A rapid method for the isolation of the thyroxine-binding globulin from only 150 ml plasma is described. The preparation of a high-activity thyroxine-sepharose is essential; this contained L-thyroxine bound exclusively by covalent linkage. Furthermore, the elution of the protein was performed under specifically hydrophobic conditions. Using isoelectric focusing on 15 individual preparations of thyroxine-binding globulin, and densitometric analysis of the polyacrylamide gels, it was possible to show three protein bands in different proportions according to the individual. Three distribution-types were found in the tested volunteers. The results of this investigation show that these types are individual-specific, whereas there are no apparent sex-specific differences.

Lupus anticoagulant after measles.

A 2 2/12 years old boy developed a "lupus anticoagulant" after measles. Fibrinogen concentration and activity of factors II, V, VII, VIII, IX, X, XI and XII were normal, but partial thromboplastin time and thromboplastin time were prolonged. Thrombin time was within the normal range. Mixing normal plasma with the patient's plasma immediately prolonged the partial thromboplastin time, and incubation of the sample did not increase the inhibition. The immunglobulin fraction prepared from the patient's plasma on DEAE-sephacel also prolonged the partial thromboplastin time in cross mixing experiments. The thrombocyte count and thrombocyte functions were normal. In spite of the pathological partial thromboplastin and thromboplastin times, surgery was performed without excessive bleeding during the operation and without delayed wound healing.

Serum haptoglobulin changes in patients with severe isolated head injury.

From a series of 74 patients with severe head injuries and massive brain lesions, we measured the changes in haptoglobulin in 33 cases. On average, the globulin was, after a short drop in the first two days, increased about three times towards the seventh day, and was still above normal after ten days. Seen together with the total alpha-2-globulin increase after head injury this rise seems mainly to be caused by the haptoglobulin changes. Haptoglobulin was found to be a good indicator of the extent of brain tissue damage. It cannot on its own be used for prediction of survival chances.

[Changes of serum proteins after craniocerebral trauma - comparison of alpha 2 and alpha 2M (author's transl)]. / Serumproteinveränderungen bei Patienten mit Schädel-Hirn-Trauma - Vergleich zwischen alpha2-und alpha2M-Globulinabweichungen

Quantitive estimations of serum proteins, including Alpha 2M globulin, from 34 patients suffering from craniocerbral trauma have been carried out. The mean value curves over a period of two weeks following trauma are presented graphically. After severe injuries, depending on the size of the cerebral lesions, an increase in Alpha 2 of prognostic significance has been observed. Levels of Alpha 2M do not correlate directly with Alpha 2 globulin, and tend to fall initially. Falls in the first three days after injury may be prognostically significant from the point of view of the prediction of a lethal outcome. There are no significant changes in the levels of total protein, albumin, Beta globulin or Gamma globulin, but Alpha 1 globulin follows the curve of Alpha 2, although to a less marked degree. Correlations between serum protease activites and increases in Alpha 2 due to enzymatically active complexes are unconnected with Alpha 2M, a decrease in which indicates increased inhibitor activity and exhaustion of the inhibitor system.

Serum globulin changes in patients with craniocerebral trauma.

Investigations of serum total protein, albumin, alpha-1, alpha-2, alpha-2M, beta- and gamma-globulin changes are reported in 48 patients with craniocerebral trauma. Only alpha-2 and alpha-2M globulins showed important variations, the first rising to three to four times normal values (112% on average) and directly correlating with the amount of tissue lesions. Alpha-2M changes were rather irregular with a tendency to severe decrease during the first days in patients with a bad prognosis. Reasons for non-regular changes of alpha-2M are discussed. Alpha-1 globulin showed a similar though less marked increase. Gamma globulin, on average, was diminished in the first week.

Antioxidative vitamin treatment: effect on lipid peroxidation and limb swelling after revascularization operations.

The objective of this study was to evaluate the antioxidative properties of the multivitamin cocktail Omnibionta (alpha-tocopherol, ascorbic acid, retinol, vitamin B complex) in terms of diminishing lipid peroxidation with improvement of leg edema performance after limb revascularization operations in humans. Fifty-one subjects were selected; the control group contained 27 patients and the treatment group 24 patients, who received the vitamin cocktail intravenously before the start of reperfusion. All patients suffered from acute or chronic arterial occlusive disease, except two subjects with arterial trauma. MDA-TBARS in plasma, quantified by HPLC, taken as a measure of lipid peroxidation was significantly increased (p < 0.001) in the control group 1 hour after reperfusion onset and decreased to its baseline value within the following 2 hours (0.73 +/- 0.26, 1.21 +/- 0.48, 0.99 +/- 0.48, 0.73 +/- 0.33 nmol/ml). In contrast, in the treatment group MDA-TBARS did not exceed the baseline value during the reperfusion period (0.93 +/- 0.30, 0.70 +/- 0.29, 0.65 +/- 0.23, 0.70 +/- 0.37 nmol/ml). Leg edema, expressed by extremity circumference, was significantly (p < 0.008) elevated in the control group (30.7 +/- 4.04 cm versus 35.35 +/- 4.12 cm) compared to a lack of increase in the treatment group (29.25 +/- 5.13 cm versus 29.76 +/- 5.70 cm). These results suggest that antioxidative vitamin treatment might be valuable in preventing lipid peroxidation and decreasing extremity edema.

Alteration of serum lipid values and lipoproteins by bacteria as a possible cause of artifacts in the screening of dyslipoproteinemias.

The intriguing observation of phospholipid deficiency in serum is described. The most prominent feature of sera was the completely abnormal lipoprotein electrophoretic pattern. The predominant occurrance of the phenomenon in the warm season suggested bacterial growth producing phospholipase C. B. cereus could be isolated from sera. In order to prevent these artifacts it is suggested to add 1 mg of Na2-EDTA to each ml of sample before dispatch.

Dissociation-enhanced lanthanide fluorescence immunoassay of lipoprotein(a) in serum.

Lipoprotein(a), a human serum lipoprotein structurally related to low-density lipoprotein (LDL), contains in addition to apolipoprotein B (apo B) apolipoprotein(a) [apo(a)], a glycoprotein with a strong homology to plasminogen. Lp(a) is a risk factor for coronary heart disease and ischemic cerebrovascular disease. Several immunological techniques are used to quantify Lp(a) in human serum, including radioimmunoassays, rocket immunoelectrophoresis, and enzyme-linked immunosorbent assays. Only the last method is suitable for large-scale clinical studies. We describe another solid-phase immunoassay, based on the dissociation-enhanced lanthanide fluorescence system Delfia (Wallac Oy), and outline the technical details. A polyclonal antiserum directed against Lp(a) was used as the capture antibody. Two kinds of detection antibodies were applied, a polyclonal antiserum against apo B and the polyclonal antiserum against Lp(a). The results agree excellently with the values estimated by rocket immunoelectrophoresis. This assay is easily established, measures Lp(a) in a wide concentration range, and is suitable for screening large populations.