[Molecular pathology of sarcomas. Update on the research group "Molecular Diagnosis of Sarcomas"]. / Molekularpathologie von Sarkomen. Erste Ergebnisse des Sarkomforschungsverbundes KoSar.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

Molybdenum supply of very low-birth-weight premature infants during the first months of life.

This explorative study was performed to assess basic data on the Mo metabolism of premature infants. Premature (n = 18, gestational age < or = 32 wk, birth weight < or = 1,500 g) and healthy formula-fed term infants (n = 14) were nourished and corrected for gestational age, identically. Plasma was collected at 3, 16, and 52 wk and 72 h balances were performed at 3 wk of age. In the premature infants, these investigations were preceded by two balance studies and an initial plasma collection. Increased Mo intake and low relative urinary excretion resulted in a retention of 4.4 (0.99-7.77) microg Mo/kg initially in premature infants (median, range). Parallel plasma concentrations were 5.5 (2.5-7.3) microg Mo/L, declining to 2.36 (0.73-3.87) microg Mo/L at 4 wk. Term infants rendered 1.49 (0.29-1.7) microg Mo/L (p < 0.05), with no significant differences later. It was concluded that the supplementation of formulas for premature infants with Mo should be recinded until there is evidence for its necessity. Index Entries: Mo; premature infants; trace elements; formula; nutrition.

Plasma selenium in preterm and term infants during the first 12 months of life.

The goal of the present study was to prospectively assess the plasma selenium (Se) concentrations of term and preterm infants during the first year of life in relation to gestational age and nutrition. Blood specimens were collected from orally formula-fed preterm infants (gestational age < 32 weeks, birth weight < 1500 g): 1.) in hospital and 2.) corrected for gestational age parallel to healthy term breast and formula-fed infants at the ages of 1, 4 and 12 months. All infants were fed according to a standardized nutritional concept, solids and follow-up formula were introduced at the age of 4 months. Plasma selenium in preterm infants in hospital was 11.7 (6.5-20.8) microg/l and 11.6 (8.8-16.7) microg/l at 4 weeks corrected for gestational age. At the age of 4 months plasma selenium was still significantly lower than in the other groups: Preterm infants: 17.1 (10.4-30.5) microg/l; formula-fed term infants: 31.3 (24.3-47.5) microg/l; breast-fed term infants: 45.6 (27.1-65.1) microg/l). The levels of breast-fed infants were significantly higher than those of both formula-fed groups up until the introduction of solids. Preterm infants had significantly low plasma selenium levels up until a postnatal age of at least 6 months. The levels were lower than those of term infants fed an identical unsupplemented infant formula during the first 4 months of life. These data support routine monitoring in hospital and selenium supplementation of preterm infants, preferably in hospital before discharge.

Molybdenum balance studies in premature male infants.

UNLABELLED: Despite the fact that the trace element molybdenum (Mo) is essential, there is insufficient knowledge about the demands in infancy. Mo balances were therefore assessed under consideration of formula Mo concentrations ranging from 0.125 to 2.704 micromol/l. Sixteen premature male infants participated in the investigation. Their birth weights were between 1,500 and 1,990 g, the median (range) gestational age was 34 (32-36) weeks and the post-conceptual age at the time of study 37.4 (34.1-40.6) weeks. Twenty-four balance studies were performed and the materials analysed by atomic absorption spectroscopy. Infants with a "low" Mo intake received 0.024 (0.020-0.035) micromol/ kg per day, had a urinary excretion of 0.02 (0.008-0.045) and a retention of 0.0006 (-0.03 to 0.008) micromol/kg per day. Infants with a "high" intake received 0.284 (0.227-0.487) micromol/kg per day, had a urinary excretion of 0.243 (0.118-0.378) and a retention of 0.022 (-71.1 to 141.44) micromol/kg per day. Since the median urinary excretion exceeded 60% of the Mo intake at low and high intakes, sufficient resorption but minimal retention was assessed at low intakes of Mo. CONCLUSION: In view of the limited knowledge of long-term exposure to an elevated molybdenum intake and the substantial retention observed at higher intakes, upper limits should be set for molybdenum concentrations in preterm infant formulas.

Magnesium balance studies in premature and term infants.

BACKGROUND: The knowledge of magnesium requirements of premature infants is still very limited, although it is essential for the optimal composition of suitable formulas. AIM OF THE STUDY: The study concept was 1) to assess physiological magnesium balance data of healthy term infants and longitudinal results from formula-fed premature infants and 2) to deduce conclusions on the magnesium content of the formulas. METHODS: Premature infants (n = 14, birth weight < or = 1500 g, gestational age < or = 32 weeks) were studied in conventional balance trials with 1) a semi-elemental diet (A), 2) preterm infant formula (B), and 3) infant formula (C). In addition, healthy term formula-fed (n = 11, D) and breast-fed (n = 14, E) infants were investigated. Analysis was performed by flame atomic absorption spectroscopy. RESULTS: The median magnesium intake ranged between 4.84 mg/kg x d-1 (breast-fed infants) and 16.33 mg/kg x d-1 (premature infants). The term breast-fed infants retained nearly as much magnesium as term formula-fed infants (3.37 vs. 3.97 mg/kg x d-1), due to a low percental fecal and urinary excretion. A higher magnesium retention was observed in the premature group: A: 7.97 mg/kg x d-1, B: 5.3 mg/kg x d-1, 3.) C: 5.54 mg/kg x d-1. CONCLUSION: In view of the high percental magnesium retention in formula-fed premature infants, excessive supply should be avoided. The long-term effects of lower intakes have to be monitored.

Molybdenum supplementation in phenylketonuria diets: adequate in early infancy?

BACKGROUND: Molybdenum concentrations in formulas exceed those in human milk by far. Infants with phenylketonuria require semisynthetic phenylalanine-restricted diets. Because these diets are presently supplemented with molybdenum, a study was conducted to determine whether retention and plasma concentration in the recipients are equivalent to those of healthy breast-fed infants. METHODS: Balance and plasma studies were conducted in healthy breast-fed infants (n = 17) and in patients with phenylketonuria (n = 4) at the age of 4 weeks, and the plasma investigations were repeated at the ages of 4 and 12 months. The samples were analyzed by atomic absorption spectroscopy (balance studies) and high-resolution inductively coupled plasma mass spectrometry (plasma). RESULTS: Molybdenum intake and retention in all infants with phenylketonuria were more than 18 times those of breast-fed infants. The plasma concentrations reflected these differences. A median of 0.04 microg/l was assessed in breast-fed infants at 4 weeks and less than 0.02 microg/l at 4 months of age. Comparative results of infants with phenylketonuria were 2.9 microg/l and 2.5 microg/l, respectively. There were no significant differences between the groups at 12 months of age. CONCLUSIONS: The phenylketonuria diets investigated showed excessive retention and plasma concentrations of the essential trace element molybdenum in early infancy. In view of these findings, the present practice of molybdenum fortification should be revised.

[Sodium and potassium metabolism in infancy]. / Natrium- und Kaliumbilanzen im Säuglingsalter.

BACKGROUND: Recommendations for the concentration of most nutrients in infant formulas are based on their concentration in human milk. Industry succeeded in adapting sodium and potassium content in infant formulas to concentration found in human milk. Whether this adaptation affects on infants' mineral balances was studied in breast-fed and artificially-fed infants. METHODS: Sodium and potassium balances were performed in 16 term male infants from their 3rd until their 17th week of life. The balances were performed at home and comprised up to five periods in intervals of three to four weeks. Each balance period consisted of subsequent three 24 h collections of milk, stool and urine samples. Ten infants were breast-fed, six received an adapted infant formula supplemented with copper, zinc and iron. RESULTS: The breast-fed infants got a mean intake of 1 mmol Na/kg b w x day and a mean intake of 1.8 mmol K/kg b w x day. Man retention was 0.4 mmol Na and 0.7 mmol K/kg b w x day. The formula-fed infants received 1.9 mmol Na/kg b w x day and 2.1 mmol K/kg b w x day. Na- and K-retention in this group was 0.5 and 0.6 mmol/kg b w x day respectively. Although sodium intake in the formula-fed infants was nearly twice as much as in the breast-fed infants the difference in sodium retention was only small (0.4 vs 0.5 mmol/kg b w x day). The formula-fed infants got more potassium than the breast-fed infants, but potassium retention was the same in both groups. CONCLUSIONS: With the adapted infant formula of this study the artificially fed infant was as well supplied with sodium and potassium as the breast-fed infant. A further reduction of the sodium concentration seems not to be useful.

Longitudinal zinc balances in breast-fed and formula-fed infants.

Longitudinal zinc (Zn) balance studies were performed under domestic conditions in term breast-fed (n = 10), term formula-fed (n = 5; Zn concentration in the formula: 4 mg/l) and preterm formula-fed (n = 3) infants during the first 17 weeks of life. Samples of milk, urine and feces were analyzed by atomic absorption spectrometry. The median daily Zn intake in breast-fed infants decreased from 0.592 (0.457-0.829) mg Zn/kg body weight to 0.151 (0.095-0.304) mg Zn/kg body weight in the first 17 weeks of life; comparable values for bottle-fed term infants were 0.58 (0.511-0.701) and 0.674 (0.529-0.731) mg Zn/kg body weight. The median percent retention of Zn intake was 27 (-60 to 81.4)% in breast-fed infants and 21.5 (-42 to 64)% in formula-fed infants. In view of the urinary and fecal Zn losses measured, a daily intake of 0.3-0.5 mg Zn/kg body weight is considered to be sufficient to ensure a Zn retention equivalent to breast-fed infants. This requires a Zn concentration of 2-3 mg/l of Zn depending on milk volume intake.

Iron availability from an infant formula supplemented with bovine lactoferrin.

Iron balance studies were performed in 16 term infants from their 3rd until their 17th week of life. The balance studies were performed at home and comprised five periods with an interval of 3 to 4 weeks, each consisting of three 24-hour collections of milk and stool samples. Seven infants were fed an adapted infant formula supplemented with bovine lactoferrin (100 mg/100 ml) and nine received the same formula without lactoferrin. The lactoferrin supplemented group received 169 micrograms iron/kg b.w. x day and retained 63 micrograms/kg b.w. x day. The mean iron intake of infants fed with the adapted formula without supplementation of lactoferrin was 118 micrograms/kg b.w. x day. The retention of iron was 43 micrograms/kg b.w. x day. Mean percentage retention of iron in the supplemented group was 36%, in the non-supplemented group 28%.

Selenium balances in young infants fed on breast milk and adapted cow's milk formula.

Selenium intake, renal and fecal excretion, and retention were determined in 11 breast-fed term infants and in 9 term infants fed with an adapted cow's milk formula. In most cases three-day-balances were determined five times at the age of 2, 5, 8, 12, and 16 weeks. Analytical determination of selenium was by atomic absorption spectroscopy with a selenium hybrid system after wet ashing of samples. The mean breast milk concentrations of selenium show a significant decrease in the course of lactation from 31.0 micrograms/L in the first collecting period to 17.6 micrograms/L in the last one. The two formula milks contained 11.8 and 7.7 micrograms/L. Intake in the breast milk group was higher than in the formula group, whereas absolute renal and fecal excretion were essentially the same. This leads to a higher selenium retention in the breast-fed infants than in the formula-fed infants, where most of the balances are negative.

Trace element excess in PKU diets?

Knowledge of trace element requirements of infants with phenylketonuria (PKU) fed a semisynthetic diet is limited. Three infants with PKU detected early were studied longitudinally in classical balance studies for 72 h, under domestic conditions, at the ages of 2, 5, 8, 12 and 16 weeks. Iron, copper and manganese concentrations in the diet and faeces were determined by atomic absorption spectroscopy. The median concentrations in the diet (4.8 mg Fe/L, 1.7 mg Cu/L, 0.43 mg Mn/L) exceed those in human milk. This is mainly due to supplementation of the amino acid preparation used. The increased intake led to a significantly higher daily retention of Cu and Mn from the PKU-diet fed, with a median of 0.17 mg Cu/kg and 6.4 micrograms Mn/kg body weight; the median retention of Fe was 0.24 mg Fe/kg. Our results confirmed the doubts about the suitability of the present trace element supplementation in formula for infants with PKU during the first four months of life.

Longitudinal manganese and copper balances in young infants and preterm infants fed on breast-milk and adapted cow's milk formulas.

1. Mn and Cu intake and retention in twenty full-term infants and six preterm infants were studied on the basis of 72 h balances. The age of the infants was 2-16 weeks and the gestational age of the preterm infants (triplets) 34 and 36 weeks. Three nutrition schemes were pursued: breast-fed, formula-fed with unsupplemented adapted formula and formula-fed with trace element supplementation. 2. The mean Mn concentration of all breast-milk samples (n 2339) was 6.2 micrograms/l. The two formulas had similar Mn concentrations (77 and 99 micrograms/l) but had different Fe, Cu (121 and 619 micrograms/l), Zn and I contents. The mean Cu concentration in mother's milk was 833 micrograms/l. 3. The following mean daily Mn intakes and retentions (micrograms/kg) respectively were measured: breast-fed full-term 1.06 (SD 0.43) and 0.43 (SD 0.65), formula-fed full-term 14.2 (SD 3.1) and 2.8 (SD 4.8), formula-fed preterm 15.0 (SD 2.2) and 0.06 (SD 5.87). The results for Cu were 114.5 (SD 22.3) and 88.0 (SD 46.5) micrograms/kg in breast-fed, 19.8 (SD 4.2) and 4.6 (-11.5-9.6) in the unsupplemented formula-fed and 106.4 (SD 18.9) and 55.5 (SD 20.3) in the supplemented formula full-term infant group. No significant influence of the trace element contents of the formulas on the relative retention of Mn or Cu was found. 4. Young preterm infants, and to some degree young full-term infants, often had negative Mn balances caused by a high faecal excretion. The formulas with a Mn concentration below 100 micrograms/l gave a sufficient supply of Mn. Preterm infants fed on the unsupplemented formula had a marginal Cu supply and their first balances were negative (-3.8 (SD 1.8) micrograms/kg). 5. In accordance with the estimated safe and adequate daily dietary intakes (recommended dietary allowances), formula-fed infants receive much more Mn than breast-fed infants and their absolute retention is higher. 6. Cu from breast-milk had a significantly better biological availability than that from cow's milk formula. If retentions similar to those in breast-fed infants are intended, we conclude, therefore, that cow's milk formula should be fortified with Cu up to a level of at least 600 micrograms/l.