Clinical validation of dialysable calcium in relation to other methods of serum calcium measurement.

Dialysable calcium (CaD) values were measured by a simple technique not interfered with by protein bound calcium and validation attempted by comparison with concentrations of ionised calcium (CaI) and clinical categorisation. CaD values were also compared with total calcium (CaT) and albumin adjusted calcium (CaA) concentrations. The normal ranges for CaD, CaT, CaA, and CaI were calculated from the results in healthy blood donors. In 50 normal subjects CaD was more highly correlated with CaI than CaT or CaA. The effects of lying down and of venous stasis in 10 normal subjects showed that CaD was slightly influenced by posture only, whereas CaT was noticeably affected by posture and venous stasis; CaA reduced but did not abolish these effects on CaT. The correlation coefficient of CaD and CaI in patients with chronic renal failure was 0.81. CaD was compared with CaT and CaA values in 293 consecutive hospital patients; discrepant results were obtained in 14.3% and 13.0% of cases respectively and there were some clinical grounds for accepting CaD as correct in 86% and 74% of these cases. Measurement of CaD is a simple, reliable method for estimating accurately the calcium concentration free from biologically inactive protein bound calcium.     

Serum ionised calcium concentration: measurement versus calculation.

Four hundred and eighteen measurements of serum ionised calcium, total calcium, and protein concentrations were made from 47 normal volunteers, 104 patients with chronic renal failure (33 being treated conservatively and 71 with regular haemodialysis), and 83 renal transplant recipients. The serum ionised calcium concentration was measured with an Orion SS-20 meter and calculated from the total serum calcium and protein concentrations by using three formulae and a nomogram. In the normal subjects and patients undergoing regular haemodialysis, whose serum calcium concentrations were in or near the normal range, three of the calculations gave results similar to those obtained by direct measurement. In patients with conservatively treated chronic renal failure and those who had received renal transplants, however, there was poor aggrement between the methods. When patients with hypercalcaemia and hypocalcaemia from all the groups were considered separately there was again poor agreement between calculated and measured concentrations of serum ionised calcium. Of the patients whose measured concentrations of serum ionised calcium were high, 69-76% were classified as normal by the four indirect methods. We conclude that calculation of the serum ionised calcium concentrations is not an adequate substitute for direct measurement.     

Concentrations of copper, zinc and various elements in serum of patients with bronchial asthma.

In this study, serum copper, zinc, magnesium, iron and calcium concentrations were investigated in 40 patients with bronchial asthma (BA) and in 43 healthy subjects. Copper and calcium levels were found to be increased in patients with BA compared to the control group (p < 0.001 and p < 0.001 respectively). On the other hand, the serum zinc level was significantly lower in healthy subjects (p < 0.01). No changes were found in serum magnesium and iron levels in patients with BA compared to controls. In addition to various elements, certain serum proteins such as albumin, transferrin and ferritin were also assessed to determine whether there was a relationship between the elements and proteins in patients with BA. There was only a significant decrease in albumin concentration in patients with BA (p < 0.05).     

Effect of aluminium hydroxide on serum ionised calcium,immunoreactive parathyroid hormone,and aluminium in chronic renal failure.

According to the Bricker-Slatopolsky theory, secretion of parathyroid hormone (PTH) is switched on in chronic renal failure by hypocalcaemia due to phosphate retention. In an attempt to reverse this process 20 patients in preterminal renal failure (plasma creatinine 569 +/- 195 mumol/l) were given aluminium hydroxide, 3.8 g daily. They were studied for four weeks and all measurements were made at the start and weekly, except measurements of serum aluminium concentration, which were made at the start and at the end of the fourth week. Mean serum phosphate fell from 1.89 to 1.47 mmol/l (5.9 to 4.6 mg/100), mean serum calcium rose from 2.07 to 2.24 mmol/l (8.3 to 9.0 mg/100 ml), and serum ionised calcium rose from 1.07 to 1.20 mmol/l (4.3 to 4.8 mg/100 ml), but serum immunoreactive PTH did not fall. Thirteen patients had initial serum immunoreactive PTH concentrations at or near to normal and 11 were taking beta-blockers but even in those with neither explanation, PTH concentrations did not fall. Serum aluminium concentrations rose from 0.4 to 1.02 mumol/l (10.9 to 27.4 microgram/l). Aluminium hydroxide corrects serum phosphate, total calcium, and ionised calcium at the price of a rise in serum aluminium concentration; in this study it did not affect serum immunoreactive PTH. The Bricker-Slatopolsky theory still needs verification in studies of patients with chronic renal failure.     

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.     

A study of zinc distribution in human serum.

The partition of zinc in human serum between two major zinc-binding proteins, albumin and alpha2-macroglobulin, was studied in 28 control subjects and in 156 hospitalized patients. Albumin-bound zinc was both the major and the more dynamic of the serum zinc components. Over a wide range of values the concentrations of albumin-bound zinc and total serum zinc were highly correlated (r=0.91) with each other, as were concentrations of albumin and albumin-bound zinc (r=0.69). alpha2-Macroglobulin-bound zinc was not strongly correlated either with total serum zinc or with the serum concentration of alpha2-macroglobulin. Twenty-four hour urinary excretion of zinc was not correlated with any of the serum zinc parameters. To a large extent it appears that total serum zinc concentration reflects serum albumin concentration.     

Exercise heart rates at different serum digoxin concentrations in patients with atrial fibrillation.

Heart rate at rest and during increasing workloads was measured in a double blind study of 12 patients with chronic atrial fibrillation when serum concentrations of digoxin were nil and at low and high therapeutic values. Twelve normal subjects were studied for comparison. The heart rate at all levels of exercise in most patients with atrial fibrillation was not adequately controlled by any serum digoxin concentration tested despite a reduction in heart rate with increasing serum digoxin concentrations. Control of the resting heart rate, even in patients with high serum digoxin concentrations, did not ensure adequate control of the heart rate during work rates equivalent to regular daily activities.     

Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality.

Delayed hypersensitivity skin reactions to a battery of recall antigens, haemoglobin and albumin concentrations, arm-muscle circumference, and percentage of ideal weight were determined before operation in 244 patients undergoing elective major surgery. Depressed skin reactions were found in 70 patients (28%), but this group did not have significantly higher sepsis or mortality rates when compared with patients with normal reactions. Significant associations were found between depressed skin reactions and increasing age, anaemia, hypoalbuminaemia, low arm-muscle circumference, and low weight. Patients with benign and malignant disease had similar distributions of skin reactions. Hypoalbuminaemia was associated with a higher rate of serious postoperative sepsis, and hypoalbuminaemia, low arm-muscle circumference, and low weight were all associated with a higher mortality. These results suggest that the routine use of delayed hypersensitivity skin testing in the preoperative assessment of surgical patients is not justified.     

High serum level of endostatin in multiple myeloma at diagnosis but not in the plateau phase after treatment

We investigated the serum concentration of endostatin in 84 patients with multiple myeloma (MM) and in 13 healthy controls. The level of measured anti-angiogenic agent was correlated with the phase and stage of the disease, and most importantly with clinical and laboratory parameters depicting the disease activity (haemoglobin, creatinine, albumins, calcium, M-component, C-reactive protein, beta2-microglobulin, lactate dehydrogenase, stage of bone disease) as well as serum levels of pro-angiogenic cytokines such as vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor and transforming growth factor-beta. The median serum level of endostatin in MM patients was 58 ng/ml and was statistically significantly higher than in the control group (median, 40 ng/ml; p=0.015). MM patients in phase I (at diagnosis) had higher levels of endostatin (median, 69 ng/ml) than those in phase II (plateau phase after treatment) (median, 49 pg/ml; p=0.044). We did not find any statistical correlation between the level of endostatin and stage of MM according to the Durie and Salmon system. The serum concentration of endostatin in MM patients with a normal level of albumins was significantly higher than in others with hypoalbuminaemia (median, 62 ng/ml versus 39 ng/ml; p=0.033). Also, patients with a normal value of lactate dehydrogenase had a higher concentration of endostatin than those with values >425 U/l (median, 70 ng/ml versus 39 ng/ml; p=0.019). We did not show any statistical correlation between the concentration of endostatin and level of haemoglobin, creatinine, calcium, C-reactive protein, beta2-microglobulin and stage of bone disease. We failed to find positive or negative correlations between the level of endostatin and vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor and transforming growth factor-beta. The concentration of endostatin did not influence the probability of survival in MM patients in our study. In conclusion, our data indicate that endostatin has a higher level in MM patients than in healthy controls. Highest values were stated in active phases of the disease (at presentation and in progression). Different clinical and laboratory parameters generally do not influence the concentration of endostatin (except albumins and lactate dehydrogenase).     

Changes in aldosterone and cortisol secretion and serum thyroxine levels in patients with active urolithiasis

The changes in calcemia and calciuria levels following low calcium diet have been studied in 35 patients with active urolithiasis and in 20 healthy subjects. Blood serum concentrations of thyroxine, cortisol and aldosterone in basal conditions as well as cortisol and aldosterone following stimulation with synacten were determined in addition. The levels of calcemia and calciuria (2.56 +/- 0.015 mmol/l and 4.70 +/- 0.41 mmol/10 mmoles of creatinine, respectively) were found to be significantly higher in patients with active urolithiasis than in healthy subjects. In addition, in patients with urolithiasis the basal blood serum concentrations of thyroxine and aldosterone were significantly higher than in healthy subjects, while the reactivity of cortisol and aldosterone secretion to synacten stimulation was normal. The results obtained suggest the participation of the described hormonal aberrations in the pathogenesis of active urolithiasis.     

Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.

Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

Can the type of variant albumin in familial dysalbuminemic hyperthyroxinemia be determined by measuring iodothyronines in serum?

A recent report documented the existence of three putative types of variant albumin in dysalbuminemic hyperthyroxinemia (DH) and suggested that measurement of the total concentration of three iodothyronines (T4, T3 and rT3) in serum of affected subjects could aid in their differentiation. In the present report, we describe three affected subjects from a single family which DH exhibited, in addition to increased serum total T4 levels, variable changes in the concentrations of total T3 and rT3. The concentrations of the following iodothyronines were above the normal limit: T4, T3 and rT3 in the propositus, T4 and T3 but not rT3 in her sister, and T4 but not T3 and rT3 in her mother. These differences cannot be caused by structurally different types of variant albumins, because the three subjects are members of the same family. They rather correlated with the relative abundance of the variant albumin in serum of the affected family members. Although previously reported subjects with DH always had serum T4 levels above the normal limit due to the predominantly higher affinity of the variant albumin for T4, significant increases in the concentration of serum T3 and rT3, reaching at times values above the upper normal range, have also been observed. Since a number of factors, including the relative abundance of the variant albumin, influence the concentration of iodothyronines in serum, their measurement alone cannot be used to determine the inherited type of DH.     

Short communication serum copper,zinc, and calcium concentrations in lice-infested sheep

The purpose of this study was to investigate changes in serum concentration of copper, zinc, and calcium in sheep naturally infested with lice (Bovicola caprae, Linognathus africanus, Linognatus ovillus, and Linognattus pedalis). Twenty sheep naturally infested with lice and 20 healthy sheep were used as subjects. Blood samples were collected from the sheep before and 8 and 15 d after treatment with Avermectin, a veterinary antiparasitic drug. The samples were analyzed for their serum copper, zinc, and calcium concentrations by atomic absorption spectrometry. The concentrations of these elements in the infested animals were lower than in the healthy controls, mainly because the general condition of the affected sheep was poor. When the infested animals were treated with an ectoparasitic drug, the serum levels of the studied elements rose to normal ranges while the health of the animals improved.     

Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation

Chemerin is an adipokine associated with metabolic syndrome, systemic inflammation and innate immune system. It has been suggested recently that the decrease in renal function may cause an increase in serum chemerin concentration. In this paper we investigated the effect of kidney transplantation on elevated serum chemerin concentration in dialyzed patients with end stage renal disease (ESRD). Twenty five ESRD patients were tested before and 3months after the kidney transplantation. The control group was comprised of twenty one healthy subjects. Serum chemerin concentrations were measured using commercial ELISA kit, and were related to clinical status, and biomarkers of renal function. We have shown that the kidney transplantation resulted in the decrease of the serum chemerin concentration. Concomitantly, serum creatinine, blood urea nitrogen, phosphate and C-reactive protein concentrations were significantly reduced, while estimated glomerular filtration rate (eGFR), calcium and hemoglobin substantially increased. Univariate regression analysis showed that serum chemerin concentration was positively correlated with serum creatinine and phosphate concentrations and negatively correlated with eGFR. The results presented here indicate that the serum chemerin concentration in patients with ESRD normalizes after the kidney transplantation, and provide additional evidence that serum chemerin concentration is related to renal function.     

Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia.

Some discrepancies exist about the relationship between serum albumin level and the pathogenesis of osteoporosis; moreover, most of the studies available have especially concerned patients with osteoporosis, often associated with fractures. Our study, therefore, aims to investigate the presence of a relationship between serum albumin level and bone mineral density in a group of healthy women (n=650; mean age 59.0 +/- 7.4 years) who voluntarily underwent screening for osteoporosis only because they were menopausal (11.2 +/- 7.4 years since menopause) and, for comparison, in a group of outpatients (n = 44; mean age 57.6 +/- 7.0 years; 9.1 +/- 6.7 years since menopause) with hypoalbuminemia associated with diseases. The results show a lack of any relationship in healthy women between serum albumin value and bone mineral density; the lack of correlation was also shown when the postmenopausal women were down into normal, osteopenic and osteoporotic (WHO criteria) or in hypo, normal and hyperalbuminemic. The only significant parameters associated with lower bone mineral density, in fact, were age and years since menopause (p<0.0001 and p<0.0001 respectively at lumbar spine and p<0.02 and p<0.001 at femoral neck level). In the group of patients with hypoalbuminemia associated with diseases, on the other hand, a relationship between reduced bone mineral density and hypoalbuminemia was found (p<0.01 and p<0.05 respectively at lumbar spine and femoral neck). In conclusion, in healthy postmenopausal women the serum albumin level does not play a significant role in the pathogenesis of bone density reduction, which is mainly due to the number of years since menopause and advancing age. The hypoalbuminemia may be related to the reduction of bone mass only in the subjects affected by diseases associated with a significant albumin reduction.     

Low Blood Mononuclear Cell Magnesium Content and Hypocalcemia in Normomagnesemic Patients

Hypomagnesemia can cause hypocalcemia. Because less than 1% of the total body magnesium (Mg) is in extracellular fluids, however, patients may be Mg-deficient despite normal serum Mg concentrations. To determine if hypocalcemia can be seen in patients who have normal serum Mg concentrations but low intracellular Mg, we studied the serum and mononuclear cell Mg contents in 82 alcoholic subjects, 30 of whom had hypocalcemia that could not be explained by other known causes of hypocalcemia. The mononuclear cell Mg content in both hypomagnesemic and normomagnesemic patients with and without hypocalcemia was significantly lower than in normal controls. The serum Mg level did not correlate with the mononuclear cell Mg or serum calcium level, but hypocalcemic patients had a significantly lower mononuclear cell content than normocalcemic patients. Six patients underwent parenteral Mg tolerance testing as an additional measure of Mg deficiency and had increased Mg retention. The serum calcium concentration returned to normal in hypocalcemic patients who were given magnesium intravenously.     

In vivo platelet activity and serum albumin concentration in nephrotic syndrome

To clarify the relationship between serum albumin concentration and in vivo platelet activity in nephrotic syndrome, Beta-thromboglobulin (B-TG) levels and circulating platelet aggregation ratio (PAR) were determined in 25 nephrotic patients. PAR levels were significantly decreased compared with the controls and showed a positive correlation with serum albumin concentrations. The values of B-TG were high in all nephrotic patients and showed an inverse relationship with serum albumin levels. In addition, increased B-TG levels correlated with decreased PAR values. Therefore serum albumin plays a regulatory role in the activity of circulating platelets in the nephrotic syndrome. Prospective longitudinal studies must be done to elucidate the usefulness of platelet inhibitors as a prophylactic therapy of intravascular thrombosis in nephrotic patients.     

Reference values for trace and ultratrace elements in human serum determined by double-focusing ICP-MS

Reference values for trace and ultratrace elements concentrations in healthy human serum, measured by double-focusing inductively coupled plasma-mass spectrometry (ICP-MS), are presented. Blood donors from Asturias (Spain) were selected as the reference population (n=59). Blood samples were collected, after donation, taking the necessary precautions to avoid contamination. All subjects analyzed had normal renal function and nutritional status, as shown from their creatinine and albumin levels. A total number of 14 elements (Al, Ca, Cr, Mn, Fe, Co, Cu, Zn, Rb, Sr, Mo, Cd, Pb, and U) were monitored almost simultaneously. Serum samples were diluted 1+4 with ultrapure water and matrix interferences were corrected using Sc, Ga, Y, and Tl as internal standards. Fe, Cu, and Zn were also determined by isotope dilution analysis (IDA). Reference trace element concentrations intervals observed containing 95% of the reference distribution after excluding outliers are presented. Fourteen serum samples from hemodialysis patients were also analyzed for comparison. High levels of Al, Cr, Sr, Mo, Mn, Pb, U, Co, and Cu and low levels of Fe, Zn, and Rb were found in the serum samples from hemodialysis patients compared to the corresponding reference values observed in this work.