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Biomedical subjects

F Ebbesen

Publications and source records attributed to F Ebbesen.

At least 73 records · Page 4Linked to original sources

Reduced albumin binding of MADDS--a measure for bilirubin binding--in sick children.

The reserve albumin concentration for binding of MADDS (monoacetyldiaminodiphenyl sulphone) in plasma is used as a measure of the reserve albumin concentration for binding of unconjugated bilirubin. The aim of the present study was to investigate whether a reduction in the reserve albumin concentration for binding of MADDS could exist in sick children after 5 months of age, where the bilirubin binding properties of the albumin has reached the adult level. The material included 75 children, 1-15 years of age with mild infections, severe bacterial infections, acute viral hepatitis, chronic hepatic diseases or uraemia, and a control group of 22 healthy children. The reserve albumin concentration was significantly lower in children with severe bacterial infections, acute viral hepatitis, and uraemia, than in healthy children (p less than 0.01), while the reserve albumin concentration in children with mild infections and chronic hepatic diseases did not differ significantly from that of the control group (p greater than 0.05). The total albumin concentration in plasma in either of the groups of sick children did not differ significantly from that of the healthy children. The plasma concentration of unconjugated bilirubin was elevated in the group of children with acute viral hepatitis, but not enough to influence the concentration of reserve albumin for binding of MADDS to a significant degree. The reserve albumin concentration was significantly lower in children with acute viral hepatitis than in children with severe bacterial infections (p less than 0.05).

Adolescent↗

Bilirubin-displacing effect of ampicillin, indomethacin, chlorpromazine, gentamicin, and parabens in vitro and in newborn infants.

Displacement of bilirubin bound to human serum albumin by ampicillin, indomethacin, chlorpromazine, gentamicin, methylparaben, and propylparaben was investigated quantitatively. Two methods were used in vitro: measurement of bilirubin displacement by studying the rate of bilirubin oxidation with hydrogen peroxide and peroxidase and determination of the albumin reserve for binding of bilirubin by observation of the dialysis rate of an added trace amount of a deputy ligand monoacetyldapsone (p-acetamido-p'-aminodiphenyl sulfone). The latter method was also used for the determination of the albumin reserve in sera from treated newborn infants. The following doses were given: ampicillin, 100 mg/kg iv; indomethacin, 0.2 mg/kg iv; chlorpromazine hydrochloride, 0.7 mg/kg im; gentamicin sulfate, 2.5 mg/kg im. The parabens were present in injectable preparations of chlorpromazine and gentamicin and were therefore given in the following doses: methylparaben, 0.35 mg/kg, and propylparaben, 0.05 mg/kg. All drugs were given in a single dose. A few additional additives and metabolites were studied in vitro. Ampicillin, given to 19 infants, produced a small, significant decrease in plasma albumin reserve, to 82% of the pretreatment level and, thus, had a slight bilirubin-displacing effect, quantitatively consistent with a weak displacing effect measured in vitro. None of the other substances showed any measurable displacement in vivo, likewise in agreement with the results from in vitro studies.

Ampicillin↗

Postnatal changes in the ability of plasma albumin to bind bilirubin.

The plasma concentrations of total albumin, unconjugated bilirubin and reserve albumin for bilirubin binding were determined in 407 healthy infants of various age up to eight days. The albumin reserve was measured using monoacetyldiaminodiphenyl-sulfone (MADDS) as a deputy ligand for bilirubin. The fraction of albumin capable of binding bilirubin was calculated as the sum of the concentrations of bilirubin and reserve albumin, divided by the total albumin concentration. Our data showed that this fraction was low (average 0.36) and did not change during the first 24 hours of life, and in this period it was independent of the maturity of the infant, as expressed by its birth weight or gestational age. From about 24 hours of life, the fraction began to increase. This increase came to an end about 60 hours after birth, and no further changes were seen during the following five days. The level of the bilirubin-binding fraction reached 60 hours after birth was related to the maturity of the infant: It increased with increasing birth weight up to 3000 g and with increasing gestational age up to 275 days, when on an average it was about 0.58. The fraction of binding albumin was independent of the sex.

Bilirubin↗

Risk of bilirubin acid precipitation in preterm infants with respiratory distress syndrome: considerations of blood/brain bilirubin transfer equilibrium.

Twenty-six preterm infants with respiratory distress syndrome (RDS), were examined daily during the first 6 days of life. Twenty-six equally preterm but clinically well infants served as controls. In the RDS infants, plasma albumin concentration was low, hyperbilirubinemia was prolonged, plasma pH was decreased during the first two days, and the concentration of reserve albumin for binding of monoacetyldiaminodiphenylsulfone (MADDS), a deputy ligand for bilirubin, was decreased on the second throughout the sixth day, when compared with the controls. These factors concur in increasing the likelihood of bilirubin acid precipitation in RDS above the increased risk present in preterm infants. The plasma of the preterm controls was supersaturated with respect to crystalline bilirubin acid by an average factor 5 (index of plasma bilirubin toxicity = 0.7) on the first day of life, peaking at a factor 10 (index 1.0) on the third and fourth days while these factors were 10 and 20 (index 1.0 and 1.3), respectively, in the RDS infants. Two of the latter surpassed a level of 60 times supersaturation (index 1.8) where acute precipitation of amorphous bilirubin acid becomes possible.

Bilirubin↗

Comparison between two preparations of human serum albumin in treatment of neonatal hyperbilirubinaemia.

Thirty-six newborn infants with normal birth weights and with uncomplicated hyperbilirubinaemia, treated with light, were studied. At onset of phototherapy the infants received intravenously 1 g human serum albumin (HSA) per kg body weight as a 9% solution. Two different preparations of HAS were used and compared. One of these, HSAI, contained sodium caprylate and N-acetyltryptophan, 5 mmol/l of each, as stabilizers. HSAII contained only caprylate, 5 mmol/l. Nineteen infants received HSAI and seventeen infants HSAII. The reserve albumin for binding of bilirubin, measured by the [14C] MADDS method, was low in both preparations in vitro. During the infusion, the serum concentrations of albumin and reserve albumin increased and the serum unconjugated bilirubin concentration decreased, resulting in a fall in the index of plasma bilirubin toxicity in all infants. After completion of the infusion, the serum concentrations of albumin and reserve albumin declined, and a slight rise in index occurred. The increase in the serum reserve albumin concentration was markedly higher during infusion of HSAII than of HSAI. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSAI is inferior to HSAII, probably due to its content of N-acetyltryptophan.

Bilirubin↗

Low reserve albumin for binding of bilirubin in neonates with deficiency of bilirubin excretion and bronze baby syndrome.

The plasma reserve albumin concentration for binding of bilirubin was found to be low in four newborn infants with deficiency of bilirubin excretion, of whom two had the bronze baby syndrome. Thus, the risk of bilirubin encephalopathy was increased. Also the ratio of binding fraction of albumin, i.e. unconjugated bilirubin plus reserve albumin, to total albumin was low. Possible causes of the low reserve albumin concentration and the ratio are discussed.

Bile↗

Bilirubin, reserve albumin for binding of bilirubin and pH in plasma during phototherapy (ordinary and double light) of term newborn infants.

Forty-five term newborn infants with uncomplicated hyperbilirubinaemia were treated continuously with phototherapy for 24 hours. Twenty-eight infants received double light treatment and 17 infants ordinary phototherapy. During both treatments a significant decrease in the serum unconjugated bilirubin concentration, a significant increase in the serum reserve albumin concentration for binding of bilirubin determined by the [14C] MADDS method, and a significant decrease in the index of serum bilirubin toxicity occurred. The changes in these parameters were significantly greater during the double light treatment than during the ordinary phototherapy. During the treatment the fall in index was constant. No significant change in plasma pH was seen. Thus, the study gives further evidence that the risk of bilirubin encephalopathy is reduced by phototherapy and that double light treatment is in the respect superior to ordinary phototherapy. Prior to phototherapy the molar ratio in serum of unconjugated bilirubin plus reserved albumin for binding of bilirubin to albumin was only 0.60, on average, and during the treatment the increase in the serum reserve albumin concentration was less than the decrease in the serum bilirubin concentration. This can be explained either by the presence in infant serum of an unknown ligand interfering competitively or allosterically in the binding of MADDS and bilirubin to albumin, or by the existence of a foetal albumin with a lower affinity for MADDS than adult albumin.

Bilirubin↗

Effect of exchange transfusion on serum reserve albumin for binding of bilirubin and index of serum bilirubin toxicity.

Seventeen newborn infants, who received their first exchange transfusion due to hyperbilirubinaemia and/or rhesus haemolytic disease, were studied. The exchange transfusions were performed with fresh, citrated blood. During the exchange transfusion a marked increase in the serum reserve albumin concentration for binding of bilirubin measured by the [14C]-MADDS method was observed, followed by a smaller decrease after the transfusion. Plasma pH increased both during and after the exchange transfusion. During the exchange transfusion a drastic fall in index of serum bilirubin toxicity was observed, followed by a smaller increase after the transfusion. Citrate was not found to interfere in the binding of bilirubin to albumin. The results are in agreement with the clinical finding that an exchange transfusion performed with fresh, citrated blood effectively reduced the risk of bilirubin encephalopathy. The ratio in serum of binding albumin, i.e. bilirubin plus reserve albumin, to total albumin failed to be increased by the exchange transfusion, and a decrease occurred after the transfusion. These findings indicate the presence in infant serum of non-binding albumin. Donor albumin with intact binding potential is partly transformed into the non-binding variety in the course of one hour after the transfusion. In the most severely rhesus sensitized infant a drastic decline of the serum albumin binding capacity was seen during the first day of life.

Bilirubin↗

Albumin administration combined with phototherapy in treatment of hyperbilirubinaemia in low-birth-weight infants.

Fifty-nine jaundiced light treated newborn infants with low birth weight were studied. At onset of phototherapy 30 infants received 1 g human serum albumin per kg body weight as a 9% solution containing sodium caprylate and N-acetyltryptophan as stabilizers. 29 infants did not receive human serum albumin and served as controls. Blood samples were taken before initiation of the therapy and again 24 and 48 h thereafter, and the following determinations were made: Serum concentrations of unconjugated bilirubin, albumin, reserve albumin for binding of bilirubin by the [14C]-MADDS method, packed cell volume and pH. Before infusion of albumin it was found that the binding fraction of serum albumin, i.e. the sum of the serum concentrations of bilirubin-albumin and reserve albumin, constituted about half of the total serum albumin concentration. The other half was non-binding, in agreement with previous findings in neonates. The effect of albumin therapy was mainly an unexpected increase of the non-binding fraction of serum albumin, while the increase of the serum reserve albumin concentration was small and the concentration of bilirubin-albumin was not changed.

Bilirubin↗

The relationship between serum bilirubin and reserve albumin for binding of bilirubin during phototherapy of preterm infants.

Thirty-four preterm newborn infants suffering from uncomplicated hyperbilirubinaemia were studied. The infants received ordinary phototherapy continuously during 48 hours. The serum unconjugated bilirubin concentration decreased significantly during the treatment, and a significant correlation between the changes in the serum bilirubin concentration and the changes in the serum reserve albumin concentration for binding of bilirubin measured by the [14C]MADDS method was found. The regression coefficients were -0.50 and -0.48 after 24 and 48 hours of treatment, respectively. Thus, it can be concluded that the risk of bilirubin encephalopathy is reduced by phototherapy in preterm infants.

Bilirubin↗

Bone mineral content during pregnancy in epileptics on anticonvulsant drugs and in their newborns.

Bone mineral content (BMC) in the long bones was measured by photon absorptiometry in epileptic pregnant and normal pregnant women an in their newborns. The BMC (highly related to total body calcium) was completely unchanged during pregnancy in both groups. The BMC was of virtually the same order in the newborns of the epileptic mothers as in the newborns of the normal mothers. Furthermore, the development state, estimated from BMC, weight and length, was identical in the two groups of newborns. These results show that anticonvulsant osteomalacia can be held at a constant level during pregnancy, and infants born to epileptic mothers have no demonstrable demineralization of bone.

Adult↗

Bilirubin-albumin binding affinity and serum albumin concentration during intensive phototherapy (blue double light) in jaundiced newborn infants.

Thirty newborn infants with normal birth weights and uncomplicated hyperbilirubinaemia were studied. Twenty three of these were treated continuously for 24 h with intensive phototherapy (blue double light), and seven untreated infants served as controls. During the treatment the serum concentrations of total bilirubin and unbound bilirubin in diluted serum measured by the peroxidase method were markedly reduced. The binding affinity of bilirubin to its high affinity site on serum albumin was not affected. During the treatment a slight decrease of the serum albumin concentration occurred, and the possible causes of this observation are discussed.

Bilirubin↗

Evaluation of the indications for early exchange transfusion in rhesus haemolytic disease during phototherapy.

The study material consisted of 251 newborn light-treated infants with rhesus haemolytic disease (RHD) caused by anti-D. 139 infants were treated with ordinary phototherapy (white single light) and 112 infants with intensive phototherapy (blue double light). An evaluation was made as to wheter the indications for early exchange transfusion which were devised for non light-treated infants with RHD were relevant, i.e. whether unnecessary early exchange transfusions are now being performed in light-treated infants. The study showed that the indications are still relevant to infants receiving ordinary phototherapy, whereas they were judged to be inappropriate for infants treated with intensive phototherapy.

Bilirubin↗

Biochemical studies in a patient with defects in the metabolism of acyl-CoA and sarcosine: another possible case of glutaric aciduria type II.

The clinical and biochemical abnormalities in a neonate, who died in coma accompanied by severe hypoglycaemia at the age of 3 days, are described. The study of the urinary metabolic profiles of organic acids and amino acids revealed that the excretion rates of glutaric acid, isovaleric acid, isovalerylglycine, 3-hydroxyisovaleric acid and isobutyric acid were very high. Increased excretion rates were also found for 2-methylbutyric acid, adipic acid, caproylglycine, 5-hydroxycaproic acid, caproic acid and butyric acid. The amino acid, sarcosine, was excreted in enhanced amounts and the patient had lactic aciduria, whereas the excretion of 3-hydroxybutyric acid was only moderately increased. This abnormal excretion pattern is consistent with a defect in the metabolism of acyl-CoAs and sarcosine. Normal activity of glutaryl-CoA dehydrogenase was found, excluding glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I).

Acyl Coenzyme A↗

Do newborns of epileptics on anticonvulsants develop biochemical signs of osteomalacia?

In a controlled prospective study performed in 16 pregnant epileptics and nine normal pregnant controls, biochemical indices of calcium homeostasis (serum calcium, serum magnesium, serum phosphate, and serum alkaline phosphatases) were determined after 18 weeks pregnancy, at birth, 8 days and 6 months after birth. Furthermore, the same indices were measured in their newborns in the first 6 months of life. In both groups of mothers the serum alkaline phosphatase rose significantly during the pregnancy (P less than 0.001), followed by a significant fall after the births (epileptics: P less than 0.05, controls: P less than 0.001), but the epileptic mothers had significantly higher initial serum alkaline phosphatase levels than the controls (P less than 0.05). In both groups of newborns a dramatical fall in serum calcium was observed in the first day of life (P less than 0.001), followed by a normalization after 1 month. The serum alkaline phosphatases doubled between day 8 and day 30 in both groups (P less than 0.001). In the standing debate whether epileptics should be treated prophylactically with vitamin D, the present study indicates that pregnancy in epileptics does not call for extra vitamin D supply, and their newborns do not develop more severe hypocalcemia than their controls.

Adult↗

Gut transit time and lactose malabsorption during phototherapy. I. A study using lactose-free human mature milk.

Sixty newborn infants with normal birth weight suffering from uncomplicated hyperbilirubinemia were studied. They were fed human mature milk from which lactose had been eliminated, whereafter either sucrose ("sucrose milk") or lactose ("lactose milk") was added. 30 infants received ordinary phototherapy and 30 intensive phototherapy (blue double light). 15 in each group had "sucrose milk" and 15 "lactose milk". There was no significant difference between the increase in blood glucose (delta BS) by lactose tolerance tests performed before phototherapy (LTT1) and by those performed during phototherapy (LTT11), neither in infants treated with ordinary nor with intensive phototherapy. All infants had normal delta BS-LTT11, except one receiving ordinary phototherapy. There was no significant difference in gut transit time between infants having "sucrose milk" and infants having "lactose milk", neither in those treated with ordinary nor with intensive phototherapy. Gut transit time was significantly shorter in infants treated with intensive phototherapy than in infants treated with ordinary phototherapy without there being any significant difference in delta BS-LTT11. The infant with flat LTT11 may have developed lactose malabsorption during the phototherapy. Thus, lactose malabsorption is not the usual cause of the reduced gut transit time during phototherapy and must be a rare complication in phototherapy.

Bilirubin↗