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Query: HUMANGGP:021525 (albumin)
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The work reviewed here illustrates how a therapeutic procedure, exchange transfusion of newborn infants, may be used to gather information which is both of practical value to infants treated in this way and also of value in the study of human neonatal physiology. The scientific deductions that can be drawn are weakened by the uncontrolled nature of the subjects available for study but this problem can be mitigated by changing one variable at a time between two groups of clinically similar infants undergoing transfusion and paying attention only to large changes in whatever is measured. In this way it has been possible to show that the glucose of ACD blood stimulates insulin and GH secretion and that the stimulation of insulin secretion is less, and that of GH more, if the transfusion is performed via the umbilical artery rather than via the vein. Arterial transfusions may be more stressful than venous ones since they are associated with greater growth hormone, ACTH and glucocorticoid release. Citrate, the other additive in ACD blood, causes a fall in ionised plasma calcium levels resulting in a stimulation of PTH secretion and mobilisation of calcium and phosphorus. Transfusion with heparinised blood is therefore preferred by some because normoglycaemia is preserved during and for three hours after transfusion, whereas post-transfusion hypoglycaemia may occur after ACD transfusion. However, heparin transfusion causes a marked rise in plasma FFA levels which may interfere with the binding of bilirubin by albumin. In either type of transfusion the side-effects may be minimised by feeding the baby afterwards, as soon as practicable. Thyroid hormones are washed out of the infant during transfusion but normal thyroid balance is restored quickly afterwards. The temperature of the donor blood does have thermal effects on the baby but these are less than might be expected due to the rapid equilibration of donor blood temperature with that of the room. The metabolic consequences of transfusion with cold blood are less than might be anticipated due in part to the glucose infusion that is part of an ACD transfusion.
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PMID:Neonatal metabolism and endocrinology studied by exchange transfusion. 17 41

A total of 30 procedures have been carried out in two patients using a new portable, compact, dialysate-free system formed by combining 300 gms of albumin--cellulose nitrate microencapsulated activated charcoal (ACAC) in series with a small Amicon ultrafiltrator. Blood passing through the ACAC hemoperfusion system is purified of waste metabolites and toxins. Fluid removal is carried out with the hydrostatic pressure of the blood passing through the dialysate-free ultrafiltrator. Since ACAC hemoperfusion is much more efficient than hemodialysers for blood purification, the combined system with the ultrafiltrator results in a very efficient system for blood purification and fluid removal. Typical clearance data for the combined systems include: 75 ml/min for 2000--5000 MW; 112.7 ml/min for 300--1500 MW; 235 ml/min for creatinine; 240 ml/min for uric acid; 2500--2700 ml/2 hours for water removal; and 17--18 gm/2 hours for NaCl removal. Guanidines, mercaptans, and PTH are also cleared very efficiently.
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PMID:Clinical evaluation of the clearance profiles of a portable, compact, dialysate-free system incorporating microencapsulated charcoal hemoperfusion for blood purification with ultrafiltration for fluid removal. 61 87

The effects of PTH on jejunal calcium, sodium, and water transport were studied in the rat in situ. In TPTx rats, as well as in normal rats, bovine PTH induced a decrease in net calcium, sodium, and water absorption. Additionally, lumen-to-plasma calcium flux was found decreased in both groups. Stimulation of endogenous PTH secretion by calcium-poor hyperoncotic albumin resulted in a similar decrease in net calcium, sodium, and water absorption. It is suggested that PTH has a direct inhibitory effect on jejunal calcium, sodium, and water absorption.
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PMID:Effect of parathyroid hormone and volume expansion on jejunal calcium, sodium, and water transport in the rat. 89 32

The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD.
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PMID:[Clinical effects of six-month short time biofiltration]. 129 70

The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.
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PMID:Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans. 159 70

In the present study an assay reactive with the intact PTH molecule supposed to be the biological active has been used for measurements in 10 normal pregnant women during the late pregnancy and post-partum. Simultaneously serum concentrations of ionized calcium, phosphate, magnesium and albumin were determined. Serum concentrations of intact PTH were low compared to non-pregnant levels, while concentrations of ionized calcium, phosphate, magnesium (corrected) were unaffected.
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PMID:Serum concentrations of intact parathyroid hormone during late human pregnancy: a longitudinal study. 176 13

The extent to which secondary hyperparathyroidism may involute remains poorly defined. Renal transplantation offers a clinical situation in which metabolic stimuli for hyperparathyroidism are removed. To examine whether hyperparathyroidism resolves after transplantation, we evaluated 11 renal transplant recipients who had been normocalcemic 6 or more months after transplantation using a sensitive 2-site immunoradiometric assay for intact serum PTH. Nine of the 11 had PTH concentrations within the normal range. Of these 9, 6 were found to have abnormal parathyroid function when challenged with an iv calcium infusion. The other 2 patients demonstrated significantly elevated basal PTH concentrations and elevated ionized calcium despite normal total serum calcium and albumin concentrations. In both, the PTH response to infused calcium was markedly abnormal, confirming hyperparathyroidism. The estimated renal threshold phosphate concentration was low in 4 of 9 patients with normal basal PTH concentrations and in both with elevated basal PTH. Bone mineral density, measured at the radius by single photon absorptiometry and at the spine by dual energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who had normal basal PTH concentrations.
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PMID:Parathyroid function in normocalcemic renal transplant recipients: evaluation by calcium infusion. 199 4

We examined the predictive value of urea kinetics for patient outcomes in CAPD by measuring dialysis index (DI; a means of quantifying CAPD dose using urea kinetics), KT/V and normalized protein catabolic rate (PCRN) on 222 occasions in 76 new patients at the time of starting CAPD and at subsequent six month intervals. We investigated how these indices altered with time and in relation to each other, and how they correlated with a wide range of subsequent patient outcomes. DI, KT/V and PCRN all tended to decrease with time on CAPD (P less than 0.0004, less than 0.0001 and 0.0005, respectively). DI and KT/V were highly correlated with each other (r = 0.89, P less than 0.0001) and both correlated with PCRN (r = 0.57, P less than 0.0001 and r = 0.60, P less than 0.0001, respectively). DI and KT/V both correlated inversely with subsequent values for serum creatinine (P less than 0.0001), urea (P less than 0.0002), potassium (P less than 0.02) and phosphate (P less than 0.002), and directly with bicarbonate (P less than 0.0001). PCRN correlated inversely with serum creatinine (P less than 0.0002) and directly with urea (P less than 0.0001) and with the number of blood transfusions received (P less than 0.03). None of these indices correlated with levels of hemoglobin, PTH, alkaline phosphatase or albumin, or with nerve conduction velocity or any other subsequent clinical outcomes including death, technique failure, hospital days, peritonitis rate and subjective indices of fatigue, pruritus and insomnia. We conclude that the urea kinetic model is predictive of some biochemical outcomes but not of clinical outcomes in CAPD patients.
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PMID:Lack of correlation between urea kinetic indices and clinical outcomes in CAPD patients. 205 26

Indirect evidence suggests a causative role for intraperitoneal free fatty acids (FFA) in hypocalcemia associated with pancreatitis. We examined the effects of intraperitoneal injection of four naturally occurring FFAs on serum calcium in rats. Two saturated FFAs, stearate and palmitate, induced little or no hypocalcemia. Two unsaturated FFAs, oleate and linoleate, caused dramatic hypocalcemia in treated versus control rats (6.3 +/- 1.4 and 5.3 +/- 0.7 mg/dl, respectively, versus 10.1 +/- 0.6). Dose-response studies demonstrated that minute quantities of oleate (100 microliters per 250 g rat) caused marked hypocalcemia (7.2 +/- 0.3 mg/dl). Treated versus control rats also revealed a decrease in ionized calcium (3.15 +/- 0.2 versus 5.6 +/- 0.05 mg/dl) and magnesium (1.4 +/- 0.15 versus 2.0 +/- 0.10), an appropriate increase in PTH levels (1670 +/- 451 versus 396 +/- 235 pg/ml), and a fall in calcitonin levels (70.4 +/- 21.3 versus 47.5 +/- 16.4 pg/ml) but no change in albumin or phosphate levels. In vitro, the Ksp of calcium dioleate was shown to be 5.3 x 10(-8) m3/liter3; thus under physiologic conditions 100 microliters oleate binds 7.2 mg calcium, or approximately twice the total ECF ionized calcium in the rat. The amounts of intraperitoneal FFA that can easily be achieved in pancreatitis complex pathophysiologically significant amounts of calcium and may lead to severe hypocalcemia.
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PMID:Intraperitoneal free fatty acids induce severe hypocalcemia in rats: a model for the hypocalcemia of pancreatitis. 207 38

Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism.
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PMID:Parathyroid hormone and cirrhosis of the liver. 222 13


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