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Thromboembolic complications are among the most important extrarenal consequences of nephrotic syndrome (NS). In addition to deep vein thrombosis in the legs and pulmonary embolism, NS is very frequently accompanied by renal vein thrombosis. Due to enhanced procoagulatory and antifibrinolytic potential and reduced anticoagulatory potential, multifactor disruption of hemostatic equilibrium leads to hypercoagulability in NS patients, which is aggravated by an increase in blood viscosity and endothelial dysfunction. Circulating antibodies against α-enolase, a plasmin(ogen)-binding protein, and the possibility of certain molecules being renally eliminated in specific manner are discussed as reasons for the particular frequency of thromboembolic complications in patients with idiopathic membranous nephropathy. Serum albumin concentration is an indicator for the risk of thrombosis in NS patients. When applying the current KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for glomerulonephritis to NS patients with a serum albumin concentration of less than 25 g/l and at least one additional thrombogenic risk factor, primary prophylactic anticoagulation ("conditioned prophylaxis") with an orally administered vitamin K antagonist (target INR 2-3) is recommended as long as the serum albumin concentration is less than 30 g/l., (© Georg Thieme Verlag KG Stuttgart · New York.)

The second part of this overview focuses on how to assess more complex metabolic causes of acid-base imbalance. This is precisely the battlefield where most of the fiery debates between the Copenhagen, the Boston and the Stewart schools aroused. While the first part of the overview merged the practical strengths of the three different approaches, in part II it will be shown how the Stewart approach in particular helps in understanding complex metabolic acid base disorders with emphasis on the often underrated role of chloride ions or the weak acid albumin. With the Stewart diagnostic approach in mind the practitioner might wish considering therapeutic options that differ from what is suggested by the more traditional approaches. The specific diagnostic steps are integrated into a simplified algorithm and an acid-base calculator is provided.

Background: With broad acceptance of Stewart's acid-base model "hyperchloremic acidosis" is regarded as an independent form of metabolic disorder. It is unknown whether hypernatremia plays a corresponding role with respect to the development of alkalosis., Methods: A total of 201 artificially ventilated, critically ill patients were monitored for hypernatremic episodes. Inclusion criterion was a serum sodium concentration above 145 mmol/l., Results: In 20 patients a total of 78 periods of elevated plasma sodium levels lasting at least 24 h were observed. In 86% of these cases sodium and chloride concentrations were simultaneously increased. The development of alkalosis correlated with the strong ion difference (r=0.80, p<0.01) but not with the serum sodium concentration (r=-0.031, p=0.78). In cases without accompanying hyperchloremia (13%) metabolic alkalosis regularly occurred and a correlation between serum sodium concentration and base excess could be verified (r=0.66, p=0.03). Alkalosis occurred in 84.8% of cases where the strong on difference exceeded 39 mmol/l., Conclusion: From the available data hypernatremic alkalosis could not be defined as an independent metabolic disorder. In would seem more appropriate to use the term "strong ion alkalosis" in this context.

We have used the Stewart approach to typical acute and compensated acid-base disorders here. Dedicated software developed by the author is available with this article and will be of help to anyone considering analyzing his or her own patients using the Stewart approach. The Stewart approach shares analytical steps with the more traditional Siggard-Andersen method, and in most cases the two methods arrive at the same therapeutic solutions. The Stewart approach is, however, more than merely a biophysical appendix to the traditional clinical model, since metabolic acid-base disorders in particular are understood within a completely different pathophysiological framework; this results in a fresh and sometimes unexpectedly helpful perspective that highlights the functional relevance of seemingly forgotten components such as the chloride ion or albumin.

In addition to paCO(2), Stewart's acid base model takes into account the influence of albumin, inorganic phosphate, electrolytes and lactate on acid-base equilibrium. It allows a comprehensive and quantitative analysis of acid-base disorders. Particularly simultaneous and mixed metabolic acid-base disorders, which are common in critically ill patients, can be assessed. Stewart's approach is therefore a valuable tool in addition to the customary acid-base approach based on bicarbonate or base excess. However, some chemical aspects of Stewart's approach remain controversial.

Objective: Higher risks of infertility have been found in overweight women. The purpose of the present study was to explore whether protein metabolism profiles related to body mass index (BMI) and to find out whether these parameters should affect IVF/ICSI outcome., Patients and Methods: 52 patients were enrolled in this study. All patients underwent an ovarian stimulation either with recombinant follicle stimulating hormone (Gonal-F) or human menopausal gonadotropin (Menogon) after pituitary down-regulation with Goserelin (Zoladex) or Triptorelin (Decapeptyl Gyn). Five blood samples were taken: before treatment, at the beginning of ovarian stimulation, on the day of HCG injection for the ovulation induction, on the day of follicle aspiration and 14 days after embryo transfer. The blood samples were analysed with regard to the serum concentrations of total protein, albumin, total bilirubin and urea. According to the BMI values the patients were divided into two groups: BMI < 25 kg/m (2) (GI, n = 28) and BMI > 25 kg/m (2) (GII, n = 24). The results of IVF/ICSI outcome were compared in both groups., Results: In both groups, the serum concentrations of total protein, albumin, total bilirubin and urea decreased during ovarian stimulation. In GII, albumin concentration decreased significantly on the day of follicle aspiration (46.0 +/- 2.3 g/l versus 43.5 +/- 2.5 g/l, p < 0.001) and 14 days after embryo transfer (46.8 +/- 2.5 g/l versus 44.7 +/- 2.3 g/l, p < 0.002), whereas the concentration of total bilirubin was not significantly decreased on the day of HCG injection (0.57 +/- 0.29 mg/dl versus 0.49 +/- 0.26 mg/dl, p = 0.11). Furthermore, pregnancy rate in women with BMI < 25 kg/m (2) was 46.4 % and in women with BMI > 25 kg/m (2) 33.1 % (p = 0.34)., Conclusions: Serum concentrations of albumin and total bilirubin are influenced by BMI. Excess weight defined as BMI > 25 kg/m (2) has a negative impact on IVF outcome leading to decreased chances of pregnancy.

Background: The use of titanium as a biomaterial in ossicular chain reconstruction is increasing. The situation for integration of biomaterials is more difficult in the semiopen implantation site middle ear than in other parts of the body. Important for integration is the contact of the biomaterial's surface toward proteins. Studies of the integration in living tissue still have to be performed in animal experiments. Morphological examinations of explanted prostheses after clinical use complete the picture of an ossicular replacement material., Methods: Preclinical studies where performed to compare the adsorption behaviour of titanium, stainless steel and aluminum oxide toward radioactive marked albumin and native collagen type I. An animal model in the rabbit was performed to study the integration of titanium in the middle ear morphologically. Middle ear prostheses removed during revision surgery were studied as well., Results: Titanium showed an adsorption amount of 360 microgram/cm(2), stainless steel of 230 microgram/cm(2) and aluminum oxide of 500 microgram/cm(2) out of an albumin solution of 400 mg/ml. Comparing desorption the mean loss was 16 % for titanium, 21 % for stainless steel and 23 % for aluminium oxide. Reassembled collagen fibrils could be detected after adsorption in collagen type I solution by means of scanning electron microscopy. Morphological studies in animal experiments showed regular healing after implantation. Explanted prostheses from humans did not show any cellular signs of repulsion., Conclusion: The results of preclinical studies and clinical use demonstrate titanium as a useful material for ossicular reconstruction in middle ear surgery.

The enantinomers of chlormezanone (1) may be achieved by enantioselective HPLC separation with a yield of 98% using a OD-Daicel column. Both enantiomers bind to human serum albumin (HSA) at pH 7.4 to a range of 11-12%. Binding to the globuline fractions is much less (2-4%, equilibrium dialysis, validation by ultrafiltration). It could be demonstrated by means of 1H-NMR spectroscopy that 1 binds to HSA with the benzene ring as well as with the thiazanone ring. The velocity of racemization could be measured for the first time using a BSA column. The enantiomers undergo racemization at pH 7.4 and 37 degrees C with a halflife of approx. 20.5 h.

Several diseases show an impairment of vascular barrier function. In the past, we found out that topically applied plasmatic factor XIII distinctly reduced secretion tendency and improved granulation in venous ulcer. Increased vascular permeability is also discussed in patients with a long lasting diabetic status being a relevant cause of impaired local wound healing. Therefore, we introduced the topical application of factor XIII into the therapy of diabetic foot ulcer. After basic experimental investigations revealed that factor XIII significantly reduces endothelial permeability of cultured endothelial cells, the first clinically treated diabetic patients showed encouraging results, too.

Unlabelled: In order to evaluate whether caudal bupivacaine 3.1 mg/kg is associated with early central nervous system toxicity in awake infants, a clinical trial was performed., Methods: After obtaining Local Ethical Committee approval and informed parental consent, seven awake infants (postconceptual age: 36-52 wks; weight: 2.2-4.7 kg) received a caudal block with bupivacaine 3.1 mg/kg with epinephrine 5 ug/ml in the left lateral position. Before performance of the caudal block a five minute EEG registration was performed, immediately followed by an assessment of the patient's clinical status based on a scoring system of following parameters: level of consciousness; muscular tone in upper extremities, tested by flexion and extension of the elbows; and the quality of the patient's cry in response to a skin pinch. Twenty minutes after the caudal block another EEG was performed and another assessment of the clinical status of the patient. After completion of the clinical assessment blood samples were collected for determination of plasma bupivacaine, albumin and alpha-1 acid glycoprotein concentrations., Results: In six of seven infants the EEG pattern from the first to the second recording showed a shift of the general frequency spectrum towards a lower range. In two of these patients (No. 3 and 4) signs of pharmacologically induced antiepileptic effects (disappearance of sharp waves) were observed. Patients No. 2 and 6 showed signs of increased muscular activity and of suspect epileptic activity. Bupivacaine plasma concentrations ranged from 0.56-1.62 ug/ml, alpha-1 acid glycoprotein levels from 0.33-0.76 g/l and albumin levels from 25-38 g/l., Discussion: In a few patients this systemic effect was clinically also associated with what is usually classified as early central nervous system toxicity. As a result of these findings the study was stopped prematurely, due to safety reasons. The low plasma levels of bupivacaine associated with side effects in this study may have two possible explanations. First, our patients did not receive any sedative drugs or anaesthetics that could have masked symptoms or have increased the threshold for systemic effects. Second, as can be expected in this age group plasma levels of alpha-1 acidglycoprotein were low. Thus, the lower plasma concentrations of total bupivacaine observed in the present study might have been associated with a similar unbound, free concentration of bupivacaine as it is seen in older children and adults at total plasma levels of 2-4 ug/ml and at alpha-1 acidglycoprotein levels within the normal adult range. We conclude that Bupivacaine at 3 mg/kg is associated with systemic side effects in infants receiving awake caudal anaesthesia. Therefore we recommend to aim at a dose of not larger than 2 mg/kg in caudal blocks if no premedication or other sedative drugs are given simultaneously.

Using the bioreactor model developed by J. Gerlach, we examined the potential of normal human hepatocytes for application in bioartificial liver devices. From normal human donor livers 1.5 x 10(8) hepatocytes were isolated. Hepatocytes were perfused in a woven multi-compartment capillary system in serum-free culture medium containing ammoniachloride over a period of 2 weeks. These cells demonstrated a well differentiated ultrastructure with formation of junctional complexes and bile canaliculi between adjacent cells. During reactor run, a constant albumin synthesis with levels above 11 mg/ml and maintenance of urea production and lignocaine metabolism (MEGX-test) were detected. These initial results indicate that normal human hepatocytes express typical morphology and ultrastructure and are able to keep differentiated functions in suitable perfusion models. Combination of the distinct human liver cell populations might enable promotion of further specific functions (clotting factors) and induction of liver cell proliferation.

We tested the hypothesis that membrane wounding of acinar cells is one of the earliest changes during the induction of acute pancreatitis. Wounding of cell membranes was detected by the penetration of the animals own albumin into cells. The pancreatitis was induced by the intraperitoneal injection of supramaximal doses of caerulein. The controls received saline. Fifteen to 180 min. after the injection the animals were perfused with buffer followed by fixative. Frozen sections of pancreas were processed identically for immunocytological localization of albumin. The intensity of staining was quantified by image analysis. Animals receiving caerulein consistently display significantly greater (p < 0.001) anti-albumin immunostaining in the cytoplasm of acinar cells than controls. The penetration of albumin into acinar cells indicates that wounding of their plasma membrane occurs during the onset of acute pancreatitis. Wounding of membranes may allow the exit of molecules such as enzymes from the acinar cells during this period.

Aim: In a prospective randomised controlled trial the effect of preoperative normovolaemic haemodilution on coagulation, plasma viscosity and plasma protein levels was examined., Method: 50 patients undergoing gastrectomies were investigated (haemodilution group, n = 30; control group, n = 20). In the haemodilution group a haematocrit of 30% was aimed at. Blood was replaced by normovolaemic infusion of 6% hydroxyethyl starch 200/0.5., Main Results: Haematocrit, colloid osmotic pressure, total serum protein, serum albumin and platelet count were significantly decreased intra- and postoperatively in the haemodilution group compared with control group (p < 0.01). All of these showed no differences between the two groups on the 7th postoperative day. Global coagulation parameters showed dilutional influences without significant differences between the two groups. Measurements of rheological parameters showed a statistically significant decrease in plasma viscosity in the haemodilution group compared with control group (p < 0.01). Haemodilution led to a marked reduction in the use of homologous blood (1 unit/haemodilution group; 10 units/ control group). The average volume of 6% hydroxyethyl starch 200/0.5 administered per patient was 15.2 ml/kgKM/d (7.6-22.2 ml/kgKM/d) in the haemodilution group and 12.7 ml/ kgKM/d (8.4-17.7 ml/kgKM/d) in the control group., Conclusion: Haemodilution induced decreases in plasma coagulation, platelet count and plasma proteins did not cause any functional impairement and may just reflect dilution of these parameters. It seems that infusion of 6% hydroxyethyl starch 200/0.5 in an amount of 10-20 ml/kgKM/d does not result in a relevant decrease in coagulation parameters.

Of 116 pregnant patients with diabetes mellitus type 1 or gestational diabetes, 12 (10.3%) had previously suffered stillbirth, while in four (3.4%) cases spontaneous abortion after the 6th month had occurred. In these 16 cases, we examined the mean daily blood glucose concentration, glycosylated hemoglobin (HbA1c), fructosamine as well as glucose and albumin elimination via urine. These control data on carbohydrate metabolism were correlated with the intensity of gestational monitoring in relation to course of pregnancy and neonatal morbidity and/or mortality. In addition, we retrospectively analyzed the cause of prior intrauterine death. In six of eight cases evaluable, we could hereby demonstrate disturbed carbohydrate metabolism. Pregnant women with diabetes mellitus type 1 were hospitalized twice as often (on average four times) as patients with gestational diabetes (2.1 admissions on average). While five of seven type 1 diabetics were primarily admitted prior to the 20th week of gestation, the majority of gestational diabetics (7/9) were first examined by qualified medical personnel trained in the care of gestational diabetes after the 28th week of gestation. Two of nine were first diagnosed post partum. 13 of 14 patients with prepartally known diabetes demonstrated mean blood glucose values under 110 mg/dl. While one of the two patients with postpartally diagnosed diabetes suffered stillbirth once again, the other had to be delivered by emergency C-section because of fetal distress (pH art. 7.08). Our results show that adequate monitoring of carbohydrate metabolism and proper care of diabetic pregnant women can lower obstetrical/neonatal risks to more acceptable levels, especially in those patients who have had stillbirth in their prior medical history.

HbAIc and fructosamine concentrations were measured in the course of 177 nondiabetic pregnancies and compared with the corresponding values of 24 nondiabetic nonpregnant women. In all three trimesters HbAIc and fructosamine were significantly lower than the corresponding values in the nonpregnant women; HbAIc: 1st trimester 4.77 +/- 0.62%, 2nd trimester 4.38 +/- 0.59%, 3rd trimester 4.33 +/- 0.49%, p < 0.01; fructosamine 1st trimester 2.13 +/- 0.17 mmol/l, 2nd trimester 2.02 +/- 0.15 mmol/l, 3rd trimester 1.90 +/- 0.15 mmol/l, p < 0.01; nonpregnant women: HbAIc 5.13 +/- 0.41%, fructosamine 2.53 +/- 0.17 mmol/l. However, if the fructosamine is correlated to the respective total protein concentration a constant value results for the course of pregnancy. The changes in the HbAIc and fructosamine concentrations in pregnancy should be taken into account when treating pregnant diabetics.

The laser flare cell meter (LFCM) is introduced as an instrument that quantifies noninvasive anterior chamber protein. The relationship between laser flare measurement and actual protein concentration in vivo and in vitro was assessed. The intensity of light scattering by helium neon laser beam is measured by LFCM and depends on protein concentration and molecular size. Total protein, albumin and transferrin were measured using nephelometry and the Coomassie method. We tested 63 patients undergoing routine cataract surgery. Laser flare measurements were made before surgery. The mean in vivo flare was 8.25 photons/ms, standard deviation 9.57 photons/ms. Before surgery paracentesis was performed in 61 patients. In vitro aqueous flare was 10.55 +/- 7.68) photons/ms. Biochemical analysis showed a mean anterior chamber protein concentration in 51 patients of 33.65 (+/- 27.36) mg/dl, a mean albumin concentration in 38 patients of 15.78 (+/- 11.03) mg/dl, and a mean transferrin concentration in 33 patients of 2.01 (+/- 0.88) mg/dl. Up to a "cell" count of 40/0.075 mm3 there is a statistically significant correlation. Laser flare values compared with biochemical analysis showed for total protein a correlation coefficient of r = 0.695 in vivo and r = 0.753 in vitro. A "cell" count higher than 40/0.075 mm3 produces marked overestimation of protein concentration by laser flare values. There is a statistical significant linear correlation between photon count by LFCM and total aqueous protein concentration by biochemical analysis in vivo and in vitro in normal cataractous eyes.

A serum sample of an outpatient, under long-term amiodarone (AM) treatment was submitted for routine checkup of thyroid function parameters. It revealed the pattern of euthyroid dysalbuminemic hyperthyroxinemia. Since no results have been published so far covering the influence of amiodarone on the specific thyroxine binding proteins, we undertook a prospective study to investigate 28 amiodarone patients, comparing these with a series of age and sex matched euthyroid subjects. Not one amiodarone patient showed changed radio-T4 distribution against the normal group. Yet, in 3 relatives of the propositus, familial screening revealed the typical pattern of thyroid function tests and of T4 distribution in radio immune ice gel electrophoresis, respectively, proving familial dysalbuminemic hyperthyroxinemia syndrome. Thus, it is most likely that this syndrome has been prevalent already prior to the amiodarone administration and consequently amiodarone was of no influence on thyroxine transport protein patterns.

Background: Possibly early functional disruption of the blood-ocular barrier in eyes of insulin dependent type I diabetics without manifestation of retinopathy can be detected using fluorophotometry and laser flare measurement., Material and Methods: In order to evaluate blood-retinal (BRB) and blood-aqueous-barrier (BAB) permeability fluorophotometry was performed in 34 eyes of 34 insulin-dependent type-I diabetics without retinopathy, additionally the aqueous laser flare was measured. 34 normal eyes of 34 age-matched subjects served as controls., Results: BRB permeability (3.2 +/- 1.3 x 10(-7) cm/s) was increased with low significance (p = 0.019) in diabetic eyes (controls: 2.6 +/- 0.7). The permeability coefficient of BAB was found to be increased in diabetics (5.3 +/- 1.8 x 10(-4)/cm) with higher significance (controls: 3.7 +/- 0.7; p = 0.00003); laser flare values in diabetic eyes (5.0 +/- 1.2 photon counts/ms) were significantly higher than in controls (4.1 +/- 1.0; p = 0.003). In diabetics there was a significant correlation (r = 0.3; p = 0.014) between the laser flare values and the permeability coefficient of BAB., Conclusions: In type-I diabetics without retinopathy BRB permeability seems to be increased slightly as well as laser flare in the aqueous; the BAB permeability coefficient seems to be the most sensitive parameter in a beginning affection of the blood-ocular barrier.

We present a technique to measure pulmonary microvascular permeability for albumin in patients with multiple trauma by means of bronchoalveolar lavage (BAL). Routine laboratory tests for the analysis of BAL fluids are used. The results were clinically validated in 10 healthy volunteers and 12 patients with multiple trauma in a first prospective study. Additionally, another 11 severely traumatized and 24 less traumatized patients were evaluated in a second prospective study. Normal values (> 0.09 +/- 0.02), posttraumatic physiological ranges (< 0.35), and a "high risk" range (> 0.5) for pulmonary microvascular permeability for albumin were developed. There was a high correlation between the first posttraumatic values of pulmonary microvascular permeability and the required duration of intensive care treatment (r = 0.81), the duration of continuous mandatory ventilation (r = 0.78) and the mean lung injury score by Murray (r = 0.76). We conclude that the presented method is harmless and useful to describe the post-traumatic course of pulmonary microvascular permeability.

Endogenous digitalis-like factor (EDLF), an inhibitor of membrane Na+/K(+)-ATPase, is discussed to be involved in the pathogenesis of cirrhogenic portal hypertension, ascites formation and development of functional hepatorenal failure. Therefore, we investigated the serum content of this mediator in patients with liver cirrhosis Child-Pugh stage A, B, and C (n = 27) by means of enzyme immunoassay with a specific digoxin antibody. Furthermore, a correlation analysis was performed in order to find out correlations between signs of cell injury, cholestasis, synthetic cell function, ascites formation, and hepatorenal failure. Our results demonstrate that EDLF is significantly elevated in Child C cirrhosis (0.61 +/- 0.15 ng/ml) in comparison to Child A cirrhosis (0.013 +/- 0.2 ng/ml) and is also higher than in Child B cirrhosis (0.23 +/- 0.25 ng/ml). In patients without ascites EDLF (0.056 +/- 0.19 ng/ml) differs significantly from that of patients with non-complicated ascites (0.156 +/- 0.176 ng/ml) and from that of patients with therapy refractory ascites (0.66 +/- 0.17 ng/ml) or hepatorenal failure (1.56 ng/ml). There are no correlations between EDLF and renal function. Significant correlations were demonstrated for cholestasis (serum bilirubin), synthesis function (serum protein, Quick's value, cholinesterase, fibrinogen, albumin), and the degree of portasystemic encephalopathy (number connection test). We conclude that EDLF may act as a mediator in the process of progressive portal hypertension and its complications due to cirrhosis. This process of progression is caused by the inhibition of Na+/K(+)-ATPase, vasoconstriction, and endothelin secretion.

Marked changes in plasma thyroid function parameters due to medication have been described in literature. We, therefore, studied the influence of routine administration of carbamazepine and diclofenac upon the radio T3/T4 distribution to specific thyroid transport proteins as well as their maximal binding capacity (MBC) for T4. Both drugs have been found to lead to changes in T3 and T4 distribution but not to any influence upon MBC. The parameters of thyroid function mostly revealed reduced FT3 and FT4 values while bTSH was affected only by carbamazepine administration.

Significantly decreased levels of serumcholinesterase (CHE) were found in acute Crohn's disease (= CD) (3.2 +/- 1.0 KU/L) and acute ulcerative colitis (= UC) (3.54 +/- 1.6 KU/L) as compared to patients with mild or quiescient disease (CD: 5.5 +/- 1.1 KU/L; UC: 5.59 +/- 0.94 KU/L) and healthy controls (5.69 +/- 1.3 KU/L). Suppression of CHE was most evident in Crohn's colitis (2.98 +/- 1.0 KU/L) and extensive UC (2.96 +/- 1.28 KU/L). Intraindividual comparison showed an increase of CHE-levels during treatment with steroids and salicylates. There was no significant correlation to the reduced bodyweight-levels in severe IBD. Best correlations were seen between CHE/albumin (CD: r = +0.61; UC: r = +0.73) and CHE/hematocrit (CD: r = +0.50; UC: r = +0.61) in severe inflammatory bowel disease. The results of a discriminant analysis showed that CHE-levels can predict the degree of activity correctly in the majority of patients with CD and UC. It is suggested that the decrease of serumcholinesterase reflects an inhibition of liver synthesis as an acute phase response-induced by endotoxins and cytokines.

A patient suffering from refractory immunocytoma was treated with therapeutical plasmapheresis. To estimate the hemorheological risk during and at the end of the therapy, hemorheological measurements were performed. Hematocrit, aggregation index, filtration index, plasma viscosity, colloid osmotic pressure and protein concentrations were analyzed. The efficiency of the plasmapheresis treatment is demonstrated by the reduction of the plasma viscosity from 5.5 to 2.3 mPa (57% reduction) and of the filtration index from 43.9 to 29.7 (32% reduction). The colloid osmotic pressure decreased from 3.4 to 2.5 kPa (26% reduction), plasma protein concentration from 106 to 86 g/l (19% reduction) and IgM concentration from 100 to 82 g/l (18% reduction), while the albumin concentration remained constant.

Out of the blood calcium fractions know only the ionized calcium is biologically active. From the height of the total calcium level despite significant dependence no secure conclusion to the Ca++ concentration can be drawn. The level of the total calcium spreads further than that one of the ionized calcium. The up to now used mathematical approaches for the estimation of the blood Ca++ concentration also proved unsuitable; none of them provides a really better statement than the total calcium level. Thus even they represent no acceptable alternative to the Ca++ determination by means of ion-selective electrodes. The investigation by means of ion-selective electrodes. The investigation of various paraclinical sizes (total calcium, total protein, albumin, creatinine, alkaline phosphatase) in a group of patients and a control group in quality and quantity resulted in a different influence on the Ca++ level by the influential factors tested. Only by measurement of the ionized calcium the real actual condition of the calcium homoeostasis can be reflected. Therefore it is no more justified to draw diagnostically and therapeutically relevant consequences from the exclusive determination of the total calcium level.

Ultrafiltration as a Fast and Simple Method to Separate Free and Protein Bound Concentrations of Local Anesthetics/Pharmacokinetic studies following high-dose anesthesia of the axillary plexus. As many other drugs amide-type local anesthetics are protein bound in plasma. The extent of binding varies between local anesthetics. The free, non protein-bound fraction of these drugs is mainly responsible for cardiovascular and central-nervous side effects. If high doses are necessary for regional anesthetic procedures it seems reasonable to determine the pharmacological active, non protein-bound fraction in addition to the total concentration of the local anesthetic drug. Analyses of protein binding was performed using an ultrafiltration method which is discussed in this paper. Total (HPLC) and unbound plasma levels (combination of ultrafiltration and HPLC) of the local anesthetic drug in central venous blood were studied in 20 healthy orthopedic patients, undergoing plastic surgery of the upper limb (elbow, forearm, hand), over a time period of 90 min, when performing axillary plexus block with 30 ml prilocaine (CAS 721-50-6) 2% (= 600 mg). Separation of the local anesthetic fractions was achieved using the ultrafiltration system MPS-1, equipped with a YMT-membrane. These membranes have a narrow pore size retaining molecules larger than 30000 Dalton. Ultrafiltration was accomplished by subjecting 1.2 ml of plasma to centrifugation at 2000 x g for 60 min at 30 degrees C using a clinical centrifuge equipped with a 35 degree angle head rotor. The plasma samples were adjusted to physiological pH (7.40) with a sodium-potassium-phosphate buffer. The tightness of the used membrane was controlled by a micromethod for protein estimation (sensitivity 10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

After deep termic and alkaline burns of rabbit's cornea the increasing of activity of neutral trypsinlike proteases, elastase and simultaneous increasing of antitryptic activity are observed in burned part of cornea, part of cornea which is surrounding the burn, and in ciliary body, iris and aqueous humor. One week after termic burn and two weeks after alkaline burn the means of these activities began decrease. The time, when ulceration and perforation of cornea are observed, is corresponded to the period of maximal activity of proteolytic enzymes in the eye tissues. At the peripherical blood there are significant changes of level of main inhibitors of proteolysis (reactants of acute phase of inflammation -alpha 1 antitrypsin and alpha 2 macroglobulin). There are qualitative and quantitative changes of proteins content of aqueous humour in the burned eyes, which have phase characteristics and depend upon the stage of inflammation process.

Human serum albumin was non-enzymatically glycated in vitro and the glycation rate determined using an affinity chromatography method. The influence of glycation on the binding of the model ligand, dansylsarcosine, at the benzodiazepine binding site was determined with a stopped-flow method. Fluorescence time curves were recorded during the binding process. As the glycation rate increased, the association velocity constant, k2, decreased from 533.3 s-1 (glycated albumin 0.048 of total serum albumin) to 218.1 s-1 (glycated albumin 0.158 of total serum albumin). The affinity constant, KA, showed a corresponding decrease from 7.61 x 10(5) l/mol (fraction of glycated albumin 0.048) to 2.60 x 10(5) l/mol (fraction of glycated albumin 0.158). The dissociation velocity constant, however, increased from 17.3 s-1 (fraction of glycated albumin 0.048) to 19.8 s-1 (fraction of glycated albumin 0.158). The inhibition of binding probably occurs via an allosteric mechanism.

In order to ascertain the hemodynamic and biochemic effect of different colloid solutions, 60 patients scheduled for hip arthroplasty were randomly divided into two groups. Prior to surgery, acute normovolemic hemodilution was performed by withdrawal of 15 ml blood/kg bodyweight and simultaneous compensation using either 5% human albumine (HA) or 6% hydroxyethylstarch (200/0.5) (HAES), each group consisting of 30 patients. During and after the operation a decrease of hemoglobin-levels to 8 g% was accepted before autologous plus (if necessary) homologous blood was applied. Neither hemodilution nor tolerance of normovolemic anemia during the intra- and postoperative period had any negative effects on clinical course. Hemodynamics kept stable, no disorders of coagulation were observed. In addition lactate levels as well as histamin values remained within normal range during the whole investigation period (until the 10th postoperative day). There were no significant differences between the two groups; only histamine levels after albumin were up to 2.2 as high as after HAES. Colloid consumption at the day of operation was on the average 2.6 l/patient x day (HAES) and 3.11 (albumin) respectively. Colloidosmotic pressure remained constant in both groups and seemed to be independent from the kind of volume therapy. The present data demonstrate that normovolemic anemia can be tolerated during the perioperative period even when large amounts of colloid infusion are applied. HAES is an less expensive but adequate colloid solution compared to albumin.

The aim was to define blood rheology in progressive systemic scleroderma (PSS). 55 patients were compared to controls. Blood and plasma viscosity, hematocrit, red cell aggregation, and deformability were measured. Except for hematocrit, all these variables are significantly altered, indicating a loss of blood fluidity in PSS. Drugs had no obvious effect on blood rheology, but the clinical picture did. The loss of blood fluidity in PSS is suggested to play a pathophysiological role in the initiation of Raynaud phenomena, from which all patients suffered.

Reference ranges were evaluated for a new colorimetric method for the determination of fructosamine in serum. The reference group was composed of 1114 non-diabetics of both sexes including children. Reference values are only slightly affected by age and sex. In the course of childhood to adolescence fructosamine values raise and finally stabilize in adults. The small differences between both sexes have no effect on the interpretation of clinical results. Relating fructosamine values to albumin or total protein has little impact on the distribution of the values when protein values were within the reference range.

We have evaluated a new method for the determination of glycated serum proteins (fructosamines), which are elevated in diabetics. In accordance with earlier findings fructosamine depends not only on mean blood glucose but also on albumin- and total protein concentrations. Therefore fructosamine is not useful as an index of diabetic blood glucose control without consideration of an individuals albumin- or protein-concentration. We propose albumin- or protein-standardized fructosamines as new indices of diabetic control.

Fructosamine values in two groups of hypo- and hyperthyroid patients were compared with the values in a reference group of non-diabetics. In hyperthyroid patients the fructosamine values were significantly lower than in the reference group. Also the mean concentrations of albumin and total protein in serum are significantly lower for hyperthyroid patients compared to hypothyroid patients. The results do not provide evidence for a simple relationship between fructosamine and protein values in these patient groups. Therefore we do not recommend to relate fructosamine to protein or albumin using correction factors. Under conditions of thyrotoxicosis fructosamine is no reliable indicator of previous serum glucose concentrations. The test is not affected by monoclonal IgG gammopathy.

The influence of pH, temperature, and albumin content in the incubation medium on the vitality incubated hepatocytes was tested in vitro as well as the effects in the trypan-blue exclusion test. pH changes between 6.8 and 7.4 in the incubation medium have not any influence on the vitality of the hepatocytes or the trypan-blue exclusion test. Reduced vitality results occurred in an initial pH 7.8 in the incubation medium. The vital dye exclusion test is not useful in case of incubation temperature of 4 degrees C, since the results regarding the vitality of the hepatocytes are only apparently better. An addition of human serum albumin is necessary for a good survival of the hepatocytes during the incubation.

The serum fructosamine normal range was confirmed. Correction to protein or albumin did not significantly affect the results. Therefore, correction of fructosamine values from patients with normal protein and albumin values would not improve the clinical significance of fructosamine. Fructosamine concentrations of heparin plasma from non-diabetics also fell within the serum fructosamine normal range. The fructosamine concentration from non-diabetic dialysis patients was significantly higher and more widely distributed than that of the reference collective despite normal blood glucose concentration. Relating fructosamine to protein had no substantial effect, whereas the differences were even increased when fructosamine was related to albumin. On the present stage of knowledge it might be considered to establish a reference interval for dialysis patients. It appears that the fructosamine estimation may then be successfully applied also to dialysis patients. Although dialysis resulted in hemoconcentration, the fructosamine concentration remained virtually unchanged. Referencing both values before and after dialysis to protein or albumin improved the correlation, but substantial differences were introduced as well. However, none of several parameters measured in parallel interfered to a degree which might explain such differences. In order to find a reasonable explanation for these findings further experiments are necessary.

During the last years fructosamine has been presented as a measurement of diabetic long term control, particularly a shorter half life of fructosamine was seen as an advantage over HbAlc (half life of fructosamine: 16 days, half life of HbAlc: 28 days). Due to diurnal variations of fructosamine levels especially in dependence of variations of the albumin-and protein concentrations the interpretation of this parameter was somewhat limited. Recently a new colorimetric fructosamine-assay was developed. We investigated the diurnal variations of fructosamine in 28 patients with type II diabetes. Fructosamine, glucose, albumin, total protein and creatinine were measured at the times towards 3, 6, 9, 12 a.m. and 3, 6, 9, and 12 p.m. In relation to the 6 a.m. fructosamine value (= 100%) the fructosamine levels showed a daily variation from -4% at 3 a.m. to +11% at 9 a.m. Correcting fructosamine levels with total protein or with albumin reduced the variations to -1% to +6% or -3% to +9%. Daily profiles of the new fructosamine assay show a daily variation which can be minimized by correcting with protein-or with albumin concentrations. For clinical routine the daily variations especially of the corrected fructosamine levels are neglectible.

The fructosamine normal range was established from a collective of 90 healthy individuals as 219-285 mumol/l (+/- 2s; mean 240 mumol/l). From a group of 10 diabetics day profiles of glucose, protein, albumin, and fructosamine were recorded by measuring these parameters three times per day at 8.00, 11.30, and 15.00. The fructosamine concentration was essentially constant also when related to protein or albumin. Fructosamine, HbAlc, CK, and CK-MB were determined from 12 diabetics with fresh myocard infarct (7 diabetics, 5 non-diabetics). Surprisingly, diabetics as well as non-diabetics manifested high fructosamine concentrations. The origin of the fructosamine increase with non-diabetic myocard infarct patients is not yet known. Possibly the acute metabolic disorder plays an important role. An influence of fibrinogen on fructosamine is also conceivable. Additional investigations, including therapy of lysis, will be carried on. The stability of the fructosamine was examined by storing 50 sera (fructosamine 295-491 mumol/l, glucose 180-279 mg/dl) at different temperatures (+ 25 degrees C, + 4 degrees C, - 20 degrees C). At - 20 degrees C and + 4 degrees C fructosamine increases by up to 2% in 24 hours. At + 25 degrees C a 6% increase in fructosamine was observed within the same observation period.

The concentrations of high molecular weight blood constituents are influenced by the increased intravascular pressure at sample collection. The impact on the fructosamine concentration was compared with that on total protein, plasma protein, electrolytes, and protein bound analytes such as calcium. The results show that fructosamine concentration behaves similar to that of total protein and albumin with change in resting position and venous-stasis.

Fructosamine values are notably influenced by plasma protein concentration. Total protein concentration in addition to variations in the plasma protein concentrations (Dysproteinemia) play a role here. This is a result of the various glycosylation of the different plasma proteins. Since fructosamine behaves similar to total protein for hypo- and hyperproteinemia, a good relationship with the total protein is expected for normoproteinemia. Hence, no erroneous high nor low fructosamine values are obtained. Dysproteinemia at normal total protein concentration causes no erroneous fructosamine values with the exception of some illnesses. Therefore, a direct relationship between protein and fructosamine at normoproteinemia is not generally necessary.

Fructosamine is thought to be an alternative diabetic long term parameter to HbAlc. A possible advantage of fructosamine is the shorter half life of this parameter. Therefore changes in the metabolic control of diabetes can be evaluated faster. However, daily variations of protein concentrations limit the clinical usefulness of fructosamine, especially in patients on hemodialysis, where we see variations in total protein- and albumin concentration during dialysis. Due to these limitations we studied the clinical usefulness of a new fructosamine assay in 38 patients with chronic renal failure. Fructosamine values, total protein, albumin, blood glucose and creatinine were measured before and after three hours hemodialysis treatment as well as glycosylated hemoglobin. Before dialysis HbA1c correlated with HbA1c after dialysis (r = 0.99), which documents the usefulness of glycosylated hemoglobin in patients on hemodialysis. Fructosamine before dialysis shows a correlation with fructosamine values after dialysis of r = 0.77. After correction with total protein the correlation was r = 0.95, also after correction with albumin. Fructosamine values before and after dialysis correlated excellently (r = 0.95). Fructosamine values before and after dialysis can only be compared after correction with total protein or with albumin.

Fructosamine, protein, albumin and HbA1c from 199 diabetics were followed for up to 220 days. An increase in average blood glucose during the preceding 10 days causes an increase in fructosamine by 50 mumol/l. During the day there is little variation in the fructosamine concentration, whereas relating fructosamine to protein or albumin results in substantial fluctuations. A possible cause is the necessity for two measurements which is associated with an increased error. Long term observations reveal a significant correlation between fructosamine and HbA1c which is little affected by relating fructosamine to protein or albumin. Diabetics exhibited significantly lower protein and albumin concentrations than the normal collective, yet the standard deviations from the individual means were only 7 and 7.9%, respectively.

In 127 patients, we investigated the influence of hyperlipemia on observed fructosamine values. An in vitro influence of the lipids on the fructosamine reading could be excluded for cholesterol, HDL-cholesterol and triglycerides. However, in patients with type I diabetes, both, cholesterol and triglycerides significantly (p less than 0.05) correlated with fructosamine. This may be explained by in vivo effects of hyperglycemia on lipids or lipoproteins. For a given level of hyperglycemia, fructosamine is slightly more sensitive than HbA1c.