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Non-invasive detection of cardiac rejection still remains a challenge after heart transplantation. We assessed troponin-T as a new serum marker to diagnose cardiac rejection. Twenty-five heart transplant patients (Berne) were monitored prospectively for up to 2 years, and compared to 89 retrospectively assessed patients (Stanford). Blood samples (392 Berne and 320 Stanford) were analyzed (creatine kinase, isoenzymes MB activity and MB mass, troponin-T and troponin-I). Regression analysis between the results of these blood samples and cardiac rejection grading from simultaneously performed endomyocardial biopsies was carried out. Troponin-T tests done in two different laboratories showed a good correlation (r = 0.91; P < 0.0001), whereas troponin-T versus troponin-I showed a lower correlation (r = 0.53; P < 0.0001). Troponin-T and -I in contrast to other enzymes were elevated for a longer period (up to 4 weeks before returning to baseline) after transplantation than during conventional cardiac surgery. Beyond 3 months the following correlations were found between troponin-T (new or old test) and the other enzymes (creatine kinase: r = 0.26, MB activity: r = 0.4, and MB mass: r = 0.68). The correlation between the degree of rejection and the enzyme release is poor, however, the best results were obtained for troponin-T (r = 0.22; P < 0.001). We found a low correlation between troponin-T and the degree of rejection beyond 3 months after heart transplantation. Despite a troponin-T elevation in some patients with rejection, the new test is not sensitive enough to be used alone for the non-invasive diagnosis of cardiac rejection.

Glucocorticoid associated altered body fat distribution and muscle wasting are well known following kidney grafting. Whether an immunosuppressive regimen after glucocorticoid withdrawal (i.e. monotherapy with cyclosporine A (CsA)) is associated with normalization of altered body fat distribution and muscle mass remains to be determined. Therefore 18 renal transplant patients (nine males and nine females, 64 +/- 5 (mean +/- SEM) months since transplantation; CsA-monotherapy: 38 +/- 7 months) and 18 age, sex and body mass index matched healthy volunteers were investigated using indirect calorimetry and dual energy X-ray absorptiometry. Lean body mass (LBM) was decreased in patients mostly due to loss of striated muscle in the legs (P < 0.01). Compared to healthy controls, fat mass was increased in head and trunk (P < 0.01) and similar in extremities. Resting energy expenditure expressed per kg LBM was increased by more than 10% (P < 0.05) in patients vs. controls. Plasma insulin and glucose concentrations, total serum cholesterol (C), triglyceride levels and the ratio of LDL-C to HDL-C were all elevated (P < 0.01) in patients as compared with controls. In summary, renal transplant patients on immunosuppressive monotherapy with CsA demonstrate decreased muscle mass despite discontinuation of prednisone therapy. The increased upper body fat might account, at least in part, for peripheral hyperinsulinaemia and dyslipidaemia observed in kidney transplant patients even years after successful transplantation.

OBJECTIVE To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of CONCLUSIONS The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

It is unclear whether insulin-dependent diabetes mellitus is a state of magnesium depletion. This is a relevant question, since magnesium deficiency has been implicated in the pathogenesis of diseases that develop to an increased extent into diabetes mellitus. Total plasma magnesium was not statistically different in 76 pediatric patients with insulin-dependent diabetes mellitus (0.77 [0.73-0.81] mmol/l; median and interquartile range), 59 healthy adults (0.80 [0.77-0.83] mmol/l) and 19 healthy children (0.80 [0.78-0.83] mmol/l). In contrast, plasma ionized magnesium, the most interesting form with respect to physiological and biological properties, was significantly lower in diabetic patients (0.50 [0.48-0.53] mmol/l) when compared with healthy adults (0.53 [0.50-0.56] mmol/l; p0.01) and healthy children (0.54 [0.51-0.56] mmol/l; p0.02). Our report confirms recent findings of reduced circulating ionized magnesium but normal circulating total magnesium in adults with non-insulin-dependent diabetes mellitus.

Cigarette smoking has been associated with increased upper body fat deposition, as estimated by the waist to hip ratio, which has been shown to be associated with glucose intolerance and dyslipidemia in nonsmoking subjects. Whether smoking is at the origin of central adiposity and its related metabolic disturbances is unclear. Moreover, it is controversial whether smoking influences fuel metabolism. Therefore, young healthy male volunteers smoking more than 10 cigarettes/day for more than 5 yr (n = 14) were compared with nonsmokers (n = 13) matched for age, sex, body mass index, alcohol consumption, physical activity, as well as family history for hypertension, diabetes, obesity, and coronary heart disease. After an overnight fast, blood was drawn for chemistry, body composition was assessed by dual energy x-ray absorptiometry, and fuel metabolism was determined by indirect calorimetry. Nicotine uptake was estimated by 24-h urinary excretion of cotinine. Lean and fat body mass as well as their respective segmental distribution (i.e. arms, trunk, legs, and head), total bone mineral content, resting energy expenditure, and fat, carbohydrate, and protein oxidation were similar between smokers and nonsmokers. In contrast, 24-h urinary cotinine excretion (72.0 +/- 11.4 vs. 0.8 +/- 0.2 mumol/L.24 h; P < 0.001), plasma glucose (4.62 +/- 0.09 vs. 4.25 +/- 0.1 mmol/L; P < 0.01), total cholesterol (4.87 +/- 0.15 vs. 4.27 +/- 0.16 mmol/L; P < 0.02), low density lipoprotein cholesterol (3.05 +/- 0.19 vs. 2.43 +/- 0.16 mmol/L; P < 0.02), and apolipoprotein B concentrations (1.09 +/- 0.11 vs. 0.83 +/- 0.03 mmol/L; P < 0.03) were all higher in smokers than in nonsmokers. In smokers, 24-h urinary cotinine excretion positively correlated with the waist to hip ratio (r = 0.58; P = 0.03) and negatively with hip circumference (r = 0.87; P < 0.001). Moreover, 24-h cotinine excretion positively correlated with fat oxidation (r = 0.57; P = 0.03), but was independent of the other metabolic parameters studied. These results suggest that the dyslipidemia and glucose intolerance observed in smokers are not related to either central obesity or the amount of nicotine inhaled, but, rather, are due to some other component in cigarette smoke. In contrast, in smokers, fat oxidation increases with increasing nicotine uptake, a fact that might account for the often observed weight gain after cessation of smoking, thus suggesting different mechanisms of action of tobacco consumption on cholesterol and glucose metabolism on one side and fat oxidation on the other.

In children and adolescents the evaluation of proteinuria is cumbersome because of the need to obtain timed urine collections. The protein/creatinine ratio (using a Coomassie blue binding technique and a kinetic Jaffe reaction, respectively) measured in 134 pediatric patients with renal disease aged 2 months to 16 years correlated closely with the overnight urine protein excretion rates using the statistical approach suggested by Bland and Altman to compare methods of measuring some quantity. The upper limit of urinary protein/creatinine ratio measured in 252 healthy children and adolescents aged 4 to 19 years was shown to be 19 mg/mmol. No age-related differences in urinary protein excretion were noted in healthy subjects. The random urine protein/creatinine ratio provides an accurate assessment of quantitative protein excretion and avoids errors and difficulties associated with timed urine collection.

Since postmenopause unopposed oestrogen replacement therapy (ERT) increases the incidence of endometrial carcinoma, the addition of a progestin in non-hysterectomised women is mandatory for hormonal substitution. On the other hand, progestins have a negative influence on serum lipids and may thus put in question the benefits of the ERT with regard to the cardiovascular risk. Progestins lower HDL and increase LDL in a dose-dependent way according to their chemical structure. In the present non-randomised study, the influence of a cyclic combined oestrogen progestin substitution on the serum lipids has been measured. From a total of 90 apparently healthy postmenopausal patients, 59 received a transdermal ERT with 17 beta-Estradiol (Estraderm TTS 50), whereas 31 women obtained a daily dose of 0.625 mg conjugated equine oestrogens (CE) perorally. Additionally all patients were given 10 mg medroxyprogesterone-acetate (MPA) daily during the first 10 days of each month. After 6 months of therapy, the following changes of serum lipids, expressed as percentage of initial values, were measured: total cholesterol in the transdermal group -2.3% (n.s.), in the peroral group -11.8% (p0.00001); triglycerides -3.7% (n.s.) resp. +8.6% (n.s.); HDL cholesterol + 0.2% (n.s.) resp. -1.8% (n.s.); LDL cholesterol +1.3% (n.s.) resp. -14.8% (p0.00001). The calculated atherogenic indices showed a decrease in the peroral substituted group of -6.5% (n.s.) for the HDL/total cholesterol ratio and -14.8% (p0.002) for the LDL/HDL ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of acute beta 2-type adrenoreceptor activation with intravenous albuterol on plasma and urinary sodium, potassium, calcium, magnesium, phosphate and lithium were investigated in 9 volunteers during acute hydration. When compared with the control infusion with inactive vehicle, beta 2-type adrenoreceptor activation decreased plasma and urinary potassium and phosphate and increased the excretion of calcium and magnesium. In addition, activation of the beta 2 adrenoreceptors did not influence creatinine clearance and plasma level and the net fractional excretion of sodium but increased the fractional clearance of exogenous lithium which measures the fraction of filtered sodium delivered by the proximal tubule. The results indicate that activation of beta 2-type adrenoreceptors decreases the proximal reabsorption of sodium.

Cystic fibrosis patients are at risk for nephrotoxic effects of aminoglycosides. Fifteen cystic fibrosis patients were admitted to hospital with 18 acute exacerbations of pulmonary symptoms associated with the isolation of Pseudomonas aeruginosa from sputum. They were treated intravenously with amikacin and ceftazidime for 14 days. Urinary excretion of N-acetyl-beta-D-glucosaminidase and alpha 1-microglobulin, two markers of tubular damage, and of albumin, a marker of glomerular permeability, was studied before and during treatment. Urinary activity of N-acetyl-beta-D-glucosaminidase and excretion of alpha 1-microglobulin was normal before amikacin treatment in approximately two thirds of patients and pathologically increased at the end of the study in 95%. Urinary albumin excretion was always normal before amikacin treatment and failed to increase consistently during treatment. The pattern of urinary protein excretion observed in the study before and during treatment with amikacin indicates a selective tubular toxicity.

As fish oil has been shown to be beneficial in rheumatoid arthritis and in psoriasis, we examined whether a diet rich in fish has a similar effect on membrane and plasma lipids as a dietary fish oil supplement. Volunteers recruited by 2 rheumatology units in Switzerland formed three parallel groups eating respective diets during 2 months: a normal diet without fish; a normal diet including 700 g fish per week; a normal diet without fish but with additional fish oil (7.5 g daily). As outcome measures we determined the lipid composition of platelet-rich plasma, the serum cholesterol and triglycerides before the study and after 1 and 2 months of the designated diet. The relative amounts of both eicosapentaenoic acid and docosahexaenoic acid increased significantly in the fish oil group and in the group with the fish diet; no change was seen in the control group. The effect on triglycerides, which were low at the beginning of the study, was minor and no change in cholesterol was seen. In conclusion, 4 to 6 meals with fish per week without any other dietary changes can induce similar changes in lipids as a supplement of fish oil.

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.

The activities of various enzymes involved in glycolysis, tricarboxylic acid cycle and fatty acid oxidation were assayed in human myometrium. A gradient of the activities from fundal to cervical myometrium was observed. In contrast to studies performed in rodents, cyclic changes of glycolytic enzymes could not be detected. Hydroxyacyl-CoA-dehydrogenase (HAD) activity was higher in secretory phase myometrium and in cases with cystic hyperplasia of the endometrium than in proliferative phase myometrium. In pregnant myometrium, lactate dehydrogenase (LDH) and glycogen phosphorylase (GLP) were increased and in postmenopausal myometrium the activities of phosphofructokinase (PFK), LDH and succinate dehydrogenase (SDH) were decreased as compared to proliferative phase myometrium. We conclude that in the human myometrium, except for HAD, activities of enzymes involved in fuel metabolism are stable throughout the menstrual cycle and that only prolonged hormonal stimulation leads to alterations of some enzyme activities.

Following a 100 km race creatine kinase (CK) creatine kinase MB (CKMB) activities were serially measured in well trained athletes and compared with enzyme activities in patients with acute myocardial infarction (AMI). The half-time of disappearance of CK (CKt1/2) was 1.75 +/- 0.70 days in runners who trained within the 1st week after the race, and was 0.81 +/- 0.18 days in patients with AMI, P less than 0.005. CKt1/2 in runners was shorter (1.17 +/- 0.28 days) when no training was performed in the first postrace week. CKt1/2 was linearly correlated with age (P less than 0.01) in the runners but not in the patients. CKMBt1/2 was 1.30 and 1.11 days in two runners and 0.56 +/- 0.10 days in patients with AMI (P less than 0.05). In line with histologic and enzymatic findings in skeletal muscle of long distance runners as reported by other workers, our kinetic data provide further evidence that CK and CKMB are released from muscular compartments in runners other than those in patients with AMI.

1. Reference values for the plasma creatinine were established using the alkaline picrate method with the Greiner Selective Analyzer GSA II in relation to the Cr 51-EDTA Clearance. Individuals with normal GFR between 93 to 159 ml/min/1.73 m2 had creatinine values in men (n = 65) from 53.7 to 119.5 mumol/l (0.61 to 1.35 mg/100 ml) and in women (n = 59) from 37.7 to 107 mumol/l (0.42 to 121 mg/100 ml). 2. The creatine determinations with the GSA II were compared to those on the Technicon Analyzer, the Beckman Creatinine Analyzer, the Gemsaec-Fast Analyzer and to the enzymatic creatinine method. A good correlation (r = 0.9780-0.984) was observed. 3. With the GSA II and the enzymatic method, bilirubin showed a minor interference which was more marked with the Beckman analyzer.

The activities of six enzymes involved in energy metabolism were measured in leiomyoma specimens and in the adjacent normal myometrium from the uterus of 17 patients. In leiomyomas the specific activities of hexokinase, lactate dehydrogenase and hydroxyacyl-CoA dehydrogenase (HAD) were higher than in myometrium. The soluble protein content was lower in leiomyomas. Therefore, most of the differences of specific activities were not found when the enzyme activity was expressed per gram wet weight of tissue, except for HAD activity, which was still higher in leiomyomas (p less than 0.05). This result is compatible with increased fatty acid utilization by leiomyomas, and with the increased growth potential of such tumors.

It has been suggested that calcium homeostasis is abnormal in the vascular smooth muscle of hypertensive patients and in the bronchial smooth muscle in asthmatics. We have found the mean baseline concentration of plasma ionized calcium to be significantly lower both in 12 asthmatics with exercise-induced asthma (EIA) [1.16 ± 0.01 (SE) mmol/l, P less than 0.001] and in 20 asthmatics without EIA (1.16 ± 0.01; P less than 0.001) compared with 42 healthy subjects (1.24 ± 0.01). The mean concentrations of plasma ionized calcium were not significantly different in asthmatics with and without EIA when measured either before treadmill exercise, during the last seconds of this exercise, or 10 or 20 min after exercise but were significantly lower than in another seven healthy subjects who undertook the same exercise protocol. Total plasma calcium concentrations in the three exercising groups were not significantly different at any point in time. The results suggest that in bronchial asthma an alteration of calcium metabolism may be important, but they also suggest that there is no simple relationship between the plasma ionized calcium concentration and acute exercise-induced bronchoconstriction.

1. A mercury(II)-thiocyanate method for the determination of chloride in plasma and serum was adapted for the Greiner Electronic Selective Analyzer GSA II. A sample blank value and a partial reagent blank value were determined by omitting thiocyanate from the control system. 2. The course of the reaction was investigated. For a reaction time of 350-500 s, the response was linear between 30 and 130 mmol/l. Between 90 and 110 mmol/l, the deviation between the actual and the theoretical value is less than 1%. 3. The calibration must be checked and, if necessary, restandardized; this is probably due to variable contamination of the reagents with chloride ions. 4. Haemolysis, lipaemia and bilirubin do not interfere. Protein has no effect on the course of the reaction. 5. At concentrations around 100 mmol/l, the in series precision, expressed as the variation coefficient (%), is 0.3-0.6% for aqueous solutions, 0.4-0.8% for liquid control sera, and 0.8-1.5% for lyophilized control sera. 6. No carry over was detectable from samples containing 150 to those containing 10 mmol/l.

The placenta and the fetal membranes differ in their energy dependent functions and in their blood supply. In a search for quantitative differences in the expression of enzymes involved in energy metabolism in these tissues we measured in the placenta and in amnion and chorion the activities of enzymes involved in carbohydrate metabolism (hexokinase, phosphofructokinase, lactate dehydrogenase, glycogen phosphorylase), a tricarboxylic acid cycle enzyme (succinate dehydrogenase) and an enzyme involved in fatty acid oxidation (hydroxyacyl-CoA-dehydrogenase). The activities of succinate dehydrogenase and hydroxyacyl-CoA-dehydrogenase in the placenta were higher than those in the membranes, whereas the activities of the other enzymes assayed were lower. Lactate dehydrogenase activity was higher in the amnion than in the chorion (p less than 0.01). These results could indicate that the fetal membranes depend mainly on glycolysis for an energy supply.

The effect of diuretics on serum lipids and lipoproteins was evaluated in 23 patients with essential hypertension treated with chlorthalidone for six weeks. Compared to placebo conditions, diuretic therapy significantly increased serum beta (+8%, p less than 0.05) or low-density-lipoprotein (LP) cholesterol (+17%, p less than 0.025). Since alpha-LP or high-density-LP cholesterol was unchanged or tended to decrease slightly, there was also an increase in the beta/alpha-LP (+26%, p less than 0.025) or low/high-density-LP cholesterol (21%, p less than 0.025) ratio. Serum cholesterol (+4%), triglycerides (+3%), phospholipids and the Apo-LP A-I, A-II and B were not changed significantly. Blood pressure and plasma potassium were decreased (p less than 0.01), blood volume and serum insulin were not changed significantly, and serum glucose was increased mildly. Plasma renin, aldosterone and norepinephrine levels rose significantly (p less than 0.05), while circulating epinephrine was unaltered. Alterations in LP were not related to variations in blood pressure, blood volume, plasma electrolytes or serum glucose or insulin; and they did not correlate with chlorthalidone-induced increases in plasma renin, aldosterone or norepinephrine. Treatment with certain diuretics may have an adverse influence on lipoprotein metabolism.

Plasma fructosamine was determined in 41 patients with acute coronary heart disease (acute myocardial infarction and instable angina) to assess its usefulness as a screening method for diabetes mellitus. The results (11/15 true positive and 23/26 true negative) were comparable to those for glycated hemoglobin (14/15, 22/26). Discriminant analysis was performed to extract additional information from further laboratory data (glucose and albumin).

A simple photometric procedure was developed for the determination of thiocyanate (SCN-) in plasma and saliva without deproteinisation or dialysis. Fe(III) ions form a red coloured complex with SCN- with a maximum absorbance at 460 nm. Mercury(II) nitrate is used to run a sample blank. A manual and an automated version (COBAS BIO) of the method is described. The method is linear up to 5000 mumol/l SCN-. The CV of the between-run precision is 2.8-8% for the manual and 2.6-6.6% for the automated method. The SCN- plasma concentration was 21-134 mumol/l in nonsmokers and 44-260 mumol/l in smokers. In mixed saliva, the concentration is much higher than in plasma: 1.57-5.5 mumol/l in smokers and 0.79-3.9 mumol/l in nonsmokers. Plasma, but not oral fluid SCN-, is a valuable parameter for studying smoking habits in population surveys. However, its use is limited. In our experience only heavy smokers can be distinguished from nonsmokers.

Many, mostly congenital, hyperammonemic syndromes may occur in the first days of life. For the diagnosis of these disorders plasma ammonia levels physiologically present in neonates and early childhood should be known, preferably by the use of an enzymatic method. Full-term newborns had higher capillary ammonia concentrations on the first day of life (30–144 μmol/l) than on the fifth day (31–104 μmol/l). In the same individuals the arterial (38–89 μmol/l) are lower than the capillary concentrations (69–112 μmol/l). The venous concentrations in school children were not higher than in adults. The scatter of capillary values, however, is great. For diagnostic purposes of disorders of ammonia detoxication sampling of arterial or venous blood is preferable.

N-acetyl-beta-D-glucosaminidase activity, alpha 1-microglobulin, albumin, and creatinine were determined in urine specimens of healthy children, age 4 months up to 15 years, and of children with type I diabetes and of juvenile patients receiving amikacin, an aminoglycoside antibiotic, during severe systemic infections. All resulting values were expressed per g of creatinine. beta-Glucosaminidase activity was determined colorimetrically using 3-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide as a substrate. Creatinine was determined by a modified Jaffé reaction. alpha 1-microglobulin and albumin were measured by immunodiffusion. In normal urine beta-glucosaminidase activity showed a log-normal distribution with an upper limit 97.5 percentile of 3.61 U/g creatinine. In patients receiving amikacin for up to 3 weeks beta-glucosaminidase and alpha 1-microglobulin significantly rose to very high values (6-10 times) during the course of the treatment. Urinary albumin values was only doubled. All values returned to normal, days or occasionally weeks after discontinuation of the therapy. 3 groups of diabetic children could be distinguished using urinary beta-glucosaminidase as a discriminator a) children with repeatedly normal activities, b) children with intermittently elevated activities and c) children with repeatedly elevated activities. While alpha 1-microglobulin concentrations followed the same pattern, the excretion of albumin did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic hypophosphatemia in humans is associated with a slow depletion of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) in erythrocytes, combined with shape alteration, impaired deformability, and viability of the cells. Likewise, incubation of erythrocytes in alkaline solution is associated with ATP depletion. Since in hyperventilation both hypophosphatemia and alkalosis are present, we have investigated red cell organic phosphates, shape, deformability, and osmotic fragility before, during, and after 20 min of voluntary hyperventilation. On the average, red cell ATP decreased by 42%, the blood pH increased by 0.2 units, and plasma inorganic phosphorus decreased by 46% compared with the initial values. Red cell 2,3-DPG, shape, deformability, and osmotic fragility remained unchanged. After the end of hyperventilation ATP increased rapidly to control values in parallel with the normalization of the blood pH, whereas inorganic plasma phosphorus remained at the low level observed during hyperventilation. It is concluded that the combined effects of hypophosphatemia and alkalosis in acute hyperventilation lead to an isolated fall of red cell ATP, which occurs as rapid as after total inhibition of red cell glycolysis in vitro.