Randomised controlled trial of albumin infusion in ill preterm infants

We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level <-30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12–24hh after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (<15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in hypoalbuminaemic sick preterm infants is unlikely to alter their respiratory status.     

Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy

BACKGROUND: The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy. METHODS: Fifty-eight infants (gestational age 39.4 +/- 1.4 weeks; birth weight 3,245 +/- 435 g) were given phototherapy with similar light energy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given human albumin at 1 g/kg bodyweight, i.v., during the first 2 h of phototherapy. RESULTS: When comparing changes in total and unbound bilirubin values 0, 2, 6 and 24 h after entering the study between the albumin-treated group and the control group, there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However, there was no significant reduction in total serum bilirubin values during the study period. In the albumin-treated group, the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40 +/- 0.19, 0.41 +/- 0.20 and 0.43 +/- 0.20 microg/dL, respectively. CONCLUSIONS: The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values, the fraction that is potentially neurotoxic.     

Fosfomycin, a new antibiotic drug (author's transl)]

After i.v. injection of 25 mg/kh/BW and 50 mg/kg/BW to children age 5--6, no difference in the pharmakokinetic action can be found. The pattern of the plasma concentration allows the assumption of a 2 compartment model. There is a decrease of the plasma concentration in the steady state with a half life of 1,6 and 1,7 hours resp. The total volume of distribution is 30% of the body weight. Fosfomycin is eliminated by glomerular filtration only. The drug is not metabolished, as 98% and 95% of the dosage are recovered in active form in the urine. In premature and newborn babies there was a 1 compartment model assumed after i.v. administration of 25 mg/kg/BW. The distribution volumes with 41% of the body weight considerably greater then in older children. Elimination is again by glomerular filtration only. Plasma levels are decreasing considerably slower so that less of the drug is excreted in the 24-hour-urine. There is a sufficient penetration of the drug into the CSF. Bactericidal levels are reached within 48 hours by cumulation of the drug.     

EFFECTS OF STABILIZERS IN PREPARATIONS OF HUMAN SERUM ALBUMIN ON THE SERUM BILIRUBIN IN GUNN RATS

ABSTRACT. Commercially available preparations of human serum albumin (HSA) containing stabilizers (i.e. 16 mmol/I Na caprylate plus 16 mmol/I Na N-acetyl- dl -tryptophan) were injected either s.c., i.p. or i.v. into homozygous infant Gunn rats. 30 min and 3 hours after s.c. injection, a serum bilirubin decline which surpassed dilution by the injected volume could be ascertained. It was mainly caused by N-acetyl- dl -tryptophan since s.c. injections of appropriate amounts of this substance alone or a mixture of both components of the stabilizer without HSA brought about similar results. HSA without these stabilizers had not such an effect. It is postulated that under these conditions Na N-acetyl- dl -tryptophanate displaced bilirubin from albumin bonds. It became obvious that after s.c. injection equilibration of HSA between skin and plasma was delayed, whereas Na N-acetyl- dl -tryptophan was rapidly transported to the blood. As for Na caprylate, a displacing effect of short duration could not be excluded by the experimental arrangement used, since the metabolism of the substance in the rat is very fast. When HSA and the stabilizers entered the plasma simultaneously (i.v. injection) no effect on serum bilirubin concentration could be proved 30 min and 3 hours later. All the bilirubin and the Na N-acetyl- dl -tryptophan present in the plasma at that time can be bound to the large amount of albumin which is directly given into the circulation of the animal. 30 min after i.p. injection of HSA preparations containing stabilizers a small decrease of serum bilirubin concentration could be recognized. It was less pronounced and less persisting than after s.c. injection. Probably equilibration of HSA between peritoneum and plasma went on faster than between skin and plasma. Only for a short period a lack of albumin binding sites in the plasma of the rat pointed to a surplus of Na N-acetyl- dl -tryptophan.     

Albumin in Management of Neonatal Hyperbilirubinaemia

The effect of albumin priming on the plasma volume, intravascular bilirubin, and HBABA-binding capacity during the subsequent 2 to 4½ hours before exchange transfusion was studied in 7 jaundiced neonates with no haemolytic disease. After priming with albumin at a dose of 1·75 g/kg body weight as a 10% solution, there was a marked increase in plasma volume as well as total intravascular bilirubin and HBABA-binding capacity. However, the serum bilirubin concentration fluctuated only very slightly, largely because of the dilution effect of the expanded plasma volume. Both albumin and bilirubin gradually diffused out of the intravascular compartment again, but at the end of the observation period there was still a net gain of both.In another 20 neonates, the efficiency of exchange transfusion in removing bilirubin was compared. The efficiency was decreased by early albumin priming and enhanced by enriching the donor''s blood with albumin.It is concluded that albumin offers immediate and short-term protection against bilirubin toxicity, and albumin-priming should be useful in situations where the babies are admitted with high bilirubin levels and blood is not immediately available for exchange transfusion. Because of its effect on the plasma volume, albumin is not recommended for babies who are already hypervolaemic. If albumin is used to increase the efficiency of exchange transfusion, it should be given together with donor''s blood or shortly before the procedure.     

Follow-up study of auditory brainstem responses in infants with high unbound bilirubin levels treated with albumin infusion therapy

BACKGROUND: Several authors reported that there was a close relationship between unbound bilirubin concentrations and abnormal results of auditory brainstem responses. Full-term infants with high-unbound bilirubin concentrations who were treated with human albumin were followed to evaluate their hearing abilities by using auditory brainstem responses. METHODS: Fifty-eight infants (gestational age, 39.4 +/- 1.4 weeks; birthweight, 3,245 +/- 435 g) with high unbound bilirubin concentrations (> or = 0.9 micro g/dL) were treated with intensive phototherapy. Twenty infants (control group) received only phototherapy, while 38 others (albumin-treated group) were also given i.v. human albumin administration (1 g/kg bodyweight) during the first 2 h of phototherapy. The follow-up study of auditory brainstem responses was carried out at 6 and 12 months of age. Development quotient tests were carried out at 18 months of age. RESULTS: Abnormalities of auditory brainstem response were detected in three infants in the albumin-treated group and six infants in the control group at 6 months. Two infants in the albumin-treated group and four infants in the control group had improved at 12 months. The results of the follow-up study at 18 months of age in the both groups were normal with development quotient >85. No patients with hearing disability and cerebral palsy were clinically detected at the age of 2 years. CONCLUSION: The results suggest that albumin priming might be effective for decreasing the rate of auditory brainstem response abnormalities at 6 months.     

In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.

A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate effects of albumin infusion in ill premature neonates.

Ten normotensive premature infants with idiopathic respiratory distress syndrome, and albumin concentrations of less than 30 g/l were given 5 ml/kg of 20% salt poor albumin by infusion. Concentrations measured six hours after infusion had increased significantly and these were associated with significant reduction in weight and improvement in urine output.     

COMPARISON BETWEEN TWO PREPARATIONS OF HUMAN SERUM ALBUMIN IN TREATMENT OF NEONATAL HYPERBILIRUBINAEMIA

ABSTRACT. 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 HSA were used and compared. One of these, HSA_I, contained sodium caprylate and N-acetyltryptophan, 5 mmol/1 of each, as stabilizers. HSA_II contained only caprylate, 5 mmol/1. Nineteen infants received HSA_I and seventeen infants HSA_II. 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 HSA_II than of HSA_I. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSA_I is inferior to HSA_II, probably due to its content of N-acetyltryptophan.     

Steady state is not achieved for most plasma amino acids during 12 hours of fasting in the neonatal piglet

Kinetics studies in neonates are important to establish the requirement for amino acids and to understand the mechanisms of normal and altered metabolism. During kinetics experiments, plasma amino acid concentrations should be in steady state. Our objective was to determine whether 12 h of fasting, after parenteral or enteral feeding, resulted in a steady state in concentrations of amino acids. Two-day-old piglets were implanted with catheters (d 0), and randomly assigned to either intragastric (i.g., n = 6) or i.v. (n = 6) feeding. On d 5, piglets were fasted for 12 h. During the first 2 h, plasma concentrations of almost all amino acids declined except asparagine (i.g. and i.v.), tyrosine (i.v.), and glycine (i.v.), which increased. Only i.g. glycine did not change. Between 2 and 12 h, the only indispensable amino acids that did not change were phenylalanine (i.v.) and histidine (i.g. and i.v.). The branched-chain amino acids increased during this period (i.v. and i.g.). The greatest change was tyrosine, increasing 13% (i.v.) and 32% (i.g.) per hour. After 12 h of refeeding, glycine, serine, threonine, and asparagine concentrations were lower than baseline (p<0.05) in the i.v. group. In i.g. fed piglets, only threonine remained below baseline (p<0.05), and arginine was greater than baseline (p<0.05). Differences between i.v. and i.g. may be the result of impaired small intestinal metabolism secondary to parenteral feeding. In neonatal pigs, most plasma amino acids were unstable during 12 h of fasting. Thus, kinetics studies that require a steady state must be conducted in the fed state.     

Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion

There is increasing evidence that obesity may damage the kidney in otherwise healthy individuals. Our study investigated the effect of childhood obesity on urinary albumin and beta-2-microglobulin excretion, and the association of these with obesity-related cardiovascular risk factors. Random morning spot urine samples were collected from clinically healthy obese ( n =86; median age 12.9 years, range 8.9–17.2 years; median weight 80.6 kg, range 46.1–136.8 kg; median body mass index 30.4 kg/m², range 24.5–43.2 kg/m²) and normal weight children ( n =79; median age 13.5 years, range 10.7–14.9 years; median weight 51.0 kg, range 27.3–72.5 kg; median body mass index 18.2 kg/m², range 13.2–23.9 kg/m²). The obese children were examined for the presence of common obesity-related cardiovascular risk factors including hyperinsulinaemia, impaired glucose tolerance (IGT), dyslipidaemia, hypercholesterolaemia, and hypertension. Obese children had a significantly higher urinary albumin/creatinine ratio (U-ACR) (median 11.7 mg/g, interquartile range 12.9 mg/g versus median 9.0 mg/g, interquartile range 5.1 mg/g; P =0.003) and urinary beta-2-microglobulin/creatinine ratio (U-BMCR) (median 63.9 µg/g, interquartile range 34.7 µg/g versus median 34.6 µg/g, interquartile range 44.1 µg/g; P <0.001) than normal weight children. Among the obese children, the U-ACR was associated with fasting hyperinsulinaemia, IGT, and hypercholesterolaemia (all P <0.05), and significantly correlated with the fasting ( r =0.23, P <0.05) and 2-h ( r =0.37, P <0.001) plasma glucose levels measured during an oral glucose tolerance test. Obese children with no more than one of the features of the metabolic syndrome had significantly lower U-ACRs than obese children with two or more features (median 10.4 mg/g, interquartile range 5.8 mg/g versus median 15.3 mg/g, interquartile range 14.9 mg/g; P <0.05). Conclusion:According to our results, clinically healthy obese children have a higher degree of albuminuria and beta-2-microglobulinuria than normal weight children, indicating early renal glomerular and tubular dysfunction as a consequence of childhood obesity. The urinary albumin/creatinine ratio in the obese children was associated with certain metabolic derangements linked to obesity, and also with the clustering of features of the metabolic syndrome.     

Parenteral amino acids increase albumin and skeletal muscle protein fractional synthetic rates in premature newborn minipigs

OBJECTIVES: Early administration of parenteral amino acids increases whole body nitrogen retention in premature infants. Tracer kinetic studies suggest an increase in whole body protein synthesis as a possible mechanism for this increase in nitrogen retention. However, the effect of early parenteral amino acids on synthesis of specific proteins remains uncertain. Using premature newborn minipigs as a model for human premature newborns, we investigated the effects of parenterally administered amino acids on albumin and skeletal muscle protein fractional synthetic rates. METHODS: Fifteen Yucatan minipigs were delivered by cesarean section 6 days before the mean expected delivery date (day 106 of gestation; expected gestation, 111-113 days) and randomized to two groups immediately after birth: 7 piglets received a mixture of amino acids (0.4 g. kg. h ) and glucose (0.8 g. kg. h ) for 5 hours, and 8 piglets (control group) received glucose only. All piglets received a continuous primed infusion of 1-[ C]valine. Arterial plasma free C-valine enrichment was measured by gas chromatography/mass spectrometry, and protein synthetic rates were determined by measuring incorporation of C-valine into albumin and skeletal muscle protein using gas chromatography/combustion/isotope ratio mass spectrometry. RESULTS: Administration of amino acids increased albumin (87.0% +/- 42.1% [mean +/- SD] vs. 37.6% +/- 6.8% per 24 hours; < 0.05) and skeletal muscle fractional synthetic rates (11.60% +/- 6.9% vs. 6.5% +/- 1.5% per 24 hours; < 0.05). CONCLUSION: We conclude that parenteral amino acids increase albumin and skeletal muscle fractional synthetic rates in premature piglets on the first day of life.     

Estimation of Digoxin Dosage in VLBW Infants Using Serum Creatinine Concentrations

ABSTRACT. Digoxin steady state plasma concentrations (C_ss) and the corresponding serum creatinine concentrations were studied in 17 VLBW infants. Birth weight was in the range of 760-1500 g (mean 1068 g), gestational age ranged from 26 to 32 weeks (mean 28.7 weeks). Digoxin steady state plasma concentrations were found in the range of 0.5-6.5 μg/ml (mean 1.88 μg/ ml) during maintenance therapy with 1.6-8.4 μg/kg BW/24 h (mean 4.4 μg/kg BW724 h) given in two divided doses intravenously. No digoxin-like immunoreactive substance could be detected in the plasma of 18 infants (10 patients with a birth weight <1500 g, 8 patients with a birth weight of 2100-4 730 g) that were not treated with digoxin. The calculated digoxin clearance ranged from 0.38-4.03 ml/min/kg BW. Serum creatinine concentrations were found in the range of 35-274 μmol/l (0.4-3.1 mg/100 ml). A hyperbolic correlation may be derived from the digoxin clearance and the corresponding serum creatinine concentration. A linear relationship was observed between the dose normalized digoxin concentrations (y=C_ss/dose in 24 h) and the respective creatinine concentrations x (v=0.52x-0.05; n=17; 5=0.24; r=0.86; p<0.01). According to this equation we suggest a dosing schedule for digoxin in VLBW infants with impaired renal function. Digoxin maintenance dose is derived from the digoxin target and the creatinine serum concentration. This dose recommendation proved reliable on four VLBW infants (birth weight 770-1260 g) with decreased renal function.     

Total energy expenditure, body composition and weight gain in moderately preterm and full-term infants at term postconceptional age

AIM: To assess total energy expenditure (TEE) and body composition, i.e. total body water (TBW) and adipose tissue volume (ATV), at term age in 8 healthy preterm infants, born between gestational weeks 30 and 33, and in 9 healthy full-term newborns. METHODS: Total and subcutaneous ATVs were assessed using magnetic resonance imaging, while TEE and TBW were estimated using doubly labelled water. RESULTS: Total ATV was 272 +/- 21 and 261 +/- 56 ml/kg body weight, while subcutaneous ATV was 88.9 +/- 1.6 and 89.7 +/- 2.0% of total ATV for preterm and full-term infants, respectively. The corresponding figures for TBW (as percentage of body weight) were 67.4 +/- 2.5 and 68.1 +/- 4.1, respectively. A significant correlation between ATV/kg body weight and body weight was found for full-term (p < 0.0001) but not for preterm infants. TEE for preterm infants was 315 +/- 20 kJ/kg body weight/24 h, which was significantly higher (p < 0.05) than TEE for full-term infants (254 +/- 45 kJ/kg body weight/24 h). At the time of investigation preterm infants weighed significantly (p < 0.05) less (540 g) than full-term infants. After the time of investigation, weight gains of preterm and full-term infants were 38 +/- 12 and 24 +/- 14 g/24 h, respectively. CONCLUSION: When compared to full-term newborns, predominantly breastfed healthy preterm infants at term postconceptional age were significantly smaller, had a similar average proportion of body fat and showed catch-up growth. Their higher TEE/kg body weight can be explained by a higher growth rate and possibly also by higher physical activity.     

The renal hemodynamic effects of ibuprofen in the newborn rabbit

In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.     

Effects of cocaine on rat embryo development in vivo and in cultures

Intraperitoneal injections of 6.25, 12.5, 25, 50, and 100 mumols/kg cocaine into pregnant Sprague-Dawley rats once a day from d 0 to 19 of gestation caused a dose-dependent increase in fetal soft tissue malformations, primarily of the genitourinary tract. At 100 mumols/kg, all implants were lost and three of the five animals died after six to seven injections. At 50 and 100 mumols/kg but not at lower doses, cocaine caused a small but significant decrease in body weight and food intake. Cocaine did not affect mean fetal and placental weights, although it increased the number of runts and edematous fetuses, and did not cause skeletal malformations. After intraperitoneal injection of 50 mumols/kg, the plasma t1/2 of cocaine was 21 +/- 5 min and peak plasma concentration (1682 +/- 260 pmol/mL, measured by HPLC) was achieved in 5-10 min; a lower peak plasma concentration (486 +/- 103 pmol/mL) was achieved in 20-60 min after s.c. injection. Concentrations of dopamine, epinephrine, and norepinephrine in brains of fetuses or newborn pups (less than 12 h old) of cocaine (50 mumols/kg)-treated rats were not significantly elevated. Cocaine injections did not affect gestational duration nor the growth pattern and the locomotor activity of offspring. However, three pups born to one cocaine-treated animal died 20 d after birth. Cocaine inhibited the growth of 10.5-d-old embryos in culture in a concentration-dependent manner and was more toxic than procaine. Approximately 80% of cocaine was metabolized during a 48-h period in embryo culture medium. It is concluded that cocaine possesses teratogenic potential that may be partly independent of maternal toxicity.     

Growth and plasma amino acid concentrations in very low birthweight infants fed either human milk protein fortified human milk or a whey-predominant formula

In a prospective, study involving 20 VLBW-infants (AGA), divided into two study groups of 10 infants, we have evaluated the effects on growth and metabolism of human milk fortified with ultrafiltrated human milk protein and a whey-predominant (whey/casein = 60/40) formula containing 2 g/dl of protein. The study was initiated at a mean age of 30 days when an oral intake of 180 ml/kg/d was tolerated and continued until a weight of 2 kg was reached. The protein intake in both groups was about 3.7 g/kg/d. All infants in both groups reached intrauterine rates of growth for the age, weight gain 18.0 g/kg/d, and length 1.2 cm/week. BUN, acid-base status, total protein and albumin were normal and similar in the two groups. Plasma levels of threonine, glycine, citrulline and methionine were significantly greater in the formula-fed infants. Taurine and proline had higher concentrations in the protein fortified human milk group. There was good tolerance of protein from both sources but the differences in plasma amino acid profiles suggest that the dietary protein quality in formulas for preterm infants must be further modified, if the goal of formula feeding is to achieve metabolic indices of protein metabolism similar to those found when human milk protein is used.     

Hypoglycaemia in Childhood Diabetes II.

ABSTRACT. Hypoglycaemia (blood glucose 1.3–2.5 mmol/1) was induced in thirty diabetic children by reduction of their morning meal. Glucagon, 10 or 20 μg/kg was then given by intramuscular or subcutaneous injection. Ten min later, all signs of hypoglycaemia had disappeared and blood glucose concentrations increased by 0.7–3.3 mmol/1. Glucagon plasma concentrations at glucose nadir were low, 23±8 pmol/l, rose to 300±42 ten min after the injection and reached peak values after another ten min. Later, a slow decrease was noted. No significant difference of blood glucose or plasma glucagon concentrations were found after subcutaneous or intramuscular injections of 20 μg/kg. After 10 μg/kg, slightly lower increase of blood glucose was seen, but the clinical effect was equally good. Nausea occurred in four children given 20 μg/kg. The rise of blood glucose did not correlate to the peak glucagon concentration obtained after the injection but showed significant correlations to the lowest glucose concentration and, inversely, to the concentration of free insulin in blood at glucose nadir. It is concluded that glucagon injections are effective in hypoglycaemia in insulin-treated diabetic children and that the injection of 10–20 μg/kg gives long-standing supraphysiological concentrations which make repeated injections unnecessary.     

The effect of glucose,tolbutamide, and arginine on C-peptide release during remission in type I diabetes mellitus

The insulin secretory capacity was examined in diabetic children at the time of partial clinical remission during which their condition could be managed with low insulin therapy (<0.5 U insulin/kg body weight) and no urinary glucose excretion.The extent of the residual beta cell function in 26 children was assessed either by an i.v. arginine test, a combined i.v. glucose-i.v. arginine test, a combined i.v. tolbutamide-i.v. arginine test, or a combined oral glucose-i.v. arginine test determining the C-peptide response by calculating the area under the curve above baseline levels. Two of the children were tested repeatedly.Under the above conditions i.v. glucose and i.v. tolbutamide did not release C-peptide in diabetic children. In contrast, C-peptide secretion during arginine infusion following i.v. glucose or i.v. tolbutamide was siginficantly enhanced compared to the C-peptide secretion observed during arginine infusion alone. The C-peptide response to oral glucose was sluggish with no effect on the following arginine infusion.The results indicate that during remission in juvenile onset diabetes i.v. glucose and i.v. tolbutamide without themselves being an appropriate signal for C-peptide release amplify the response to a subsequent arginine infusion under appropriate conditions.     

26. Premature Infants Treated with Human Albumin

Total serum protein content was determined in the cord blood of 79 premature infants. There was a tendecy for the serum protein values to rise with the birth weight and gestational age. Boys had, on average, lower serum protein values than girls. 31 infants with serum protein content less than 5 g/100 ml were treated with albumin solution, 2 g per kg of body weight intravenously, on the first day of life. 27 infants, serving as controls, were not treated with albumin. The two groups showed the same frequency of "respiratory distress". One infant died in connection with the administration of albumin.