Renal excretion of calcium and phosphorus in premature infants with incipient late metabolic acidosis.

BACKGROUND: Premature infants receiving alimentation with cow milk-based formulas run a considerably high risk of incipient late metabolic acidosis, an early stage developing of manifest late metabolic acidosis. Is bone metabolism involved in pathophysiologic mechanisms characterizing this early stage of retention acidosis? METHODS: Urinary ionography was performed in 10 premature infants with spontaneous development of incipient late metabolic acidosis (indicated by urine pH < 5.4 on 2 consecutive days) and 10 pair-matched premature infants with normal values of urine pH; both groups were receiving full oral nutrition with the same standard formula. Moreover, in 37 premature infants with incipient late metabolic acidosis who were randomly allocated to oral therapy with 2 mmol. kg(-1). d(-1) of either NaHCO 3 or NaCl over a period of 7 days, urinary excretion of calcium and phosphorus was assessed on day 1 and day 7. RESULTS: Incipient late metabolic acidosis was accompanied by increased phosphaturia in premature infants receiving full oral nutrition. Seventeen premature infants receiving NaCl therapy (19 treatment periods) showed increased calciuria from day 1 to day 7, whereas, in 20 premature infants receiving NaHCO 3 therapy (23 treatment periods), calcium or phosphorus excretion in urine did not increase. CONCLUSIONS: The data of urinary calcium and phosphorus excretion in premature infants support the hypothesis that bone mineralization may already be impaired in the early stage of incipient late metabolic acidosis.

Minimal-invasive approach to study pulmonary, metabolic and renal responses to alimentary acid-base changes in conscious rabbits.

BACKGROUND: Systemic acid-base balance is maintained by the complex interplay of renal and pulmonary control functions and metabolic adaptations, whereby intake and mineral composition of feed are important factors. AIM OF THE STUDY: It was intended to explore the role of alimentary acid-base load and carbonic anhydrase activity for regulatory responses of renal, pulmonary or metabolic origin in rabbits as typical herbivores. METHODS: Sixty-eight conscious male rabbits (about 3.5 kg) were kept in a metabolic cage, to determine daily water intake, urine excretion and food consumption. Different groups were fed either alkali-rich rabbit standard pellets, or modified rabbit chow with low Ca++-content, or a special diet with very low alkali content, or standard food together with a low oral dose (about 20 mg x kg(-1) x d(-1)) acetazolamide. Samples from the central ear artery were analyzed for blood gases (PaO2, PaCO2), pHa, base excess (BE) and actual bicarbonate (HCO3a-). The metabolic CO2 production (VCO2 STPD) was determined, to calculate alveolar ventilation (VA BTPS). Anaerobically collected urine was analyzed for pHu and for concentrations of bicarbonate/carbonate (HCO3-/CO3--), ammonium (NH4+), and phosphate. RESULTS: 1) Systemic BE was not affected by alimentary alkali load, either varied spontaneously by standard food intake or by the low-Ca++ diet, and decreased only slightly on the low-alkali diet, but distinctly upon carbonic anhydrase inhibition. 2) Under all conditions of alimentation, PaCO2 was closely correlated with BE without a detectable set-point, the normal-range variability of BE being sufficient to elicit corresponding changes in VA. In contrast, acetazolamide led to much lower values of PaCO2 than predicted by the reference PCO2/BE relationship, being primarily caused by significant reductions in VCO2 (> 20%). 3) Prior to other systems, renal base excretion, normally being high on species-adapted standard chow, closely followed any variation of alimentary alkali load and approached zero upon the low-alkali diet. It was, however, not significantly influenced by carbonic anhydrase (CA) inhibition on alkalirich alimentation. CONCLUSIONS: Blood acid-base balance in rabbits is maintained over a wide range of alimentary alkali load by effective adaptation of renal base excretion, independent of CA activity. Ventilatory pH control is perpetuated even in the normal range of BE, provided metabolic rate is not impaired, e. g., by CA inhibition. These results may help one understand the different manifestations of acid-base disorders in body fluids under clinical conditions.

[3-hydroxy-3-methylglutaraciduria (case report of a female Turkish sisters with 3-hydroxy-3- methylglutaryl-Coenzyme A lyase deficiency]. / 3-Hydroxy-3-methylglutaracidurie (Fallbeschreibung eines weiblichen türkischen Geschwisterpaares mit 3-Hydroxy-3-methylglutaryl-Coenzym A Lyase Mangel).

3-Hydroxy-3-methylglutaric aciduria is a rare inborn error of metabolism, caused by reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase. We describe two turkish sisters with this disease. In the older sister clinical symptoms with lethargy, convulsions, metabolic acidosis, hypoglycemia and hyperammonemia lead to the diagnosis. The younger sister was diagnosed prenatally. The clinical course of our patients is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and therapeutic regimens.

[Trisomy of the short arm of chromosome 10p; description of a female patient with de novo duplication 10p11.2-15]. / Trisomie des kurzen Arms von Chromosom 10p; Beschreibung einer Patientin mit de novo Duplikation 10p11.2-15.

Trisomy 10p is a rare chromosomal syndrome, characterized by craniofacial abnormalities, malformations of organs and skeleton, and impaired psychomotor development. In most of the cases partial trisomy 10p results of a balanced translocation or inversion, the mother being carrier of the structural abnormality. Only eight of 63 patients with trisomy 10p found in a literature survey present a de novo trisomy. 17 cases show a pure trisomy 10p without an associated deficiency of any other chromosome segment. We report a female patient with an interchromosomal de novo duplication 10p11.2-->15, demonstrating typical clinical signs like craniofacial abnormalities, oral cleft, club foot, seizures, and a severe delay of psychomotor development.

[Polysaccharide specific humoral immunodeficiency in ectodermal dysplasia. Case report of a boy with two affected brothers]. / Polysaccharid-spezifischer humoraler Immundefekt bei ektodermaler Dysplasie. Fallbericht über einen Jungen mit zwei betroffenen Brüdern.

We report a now three year old male patient with ectodermal dysplasia and a polysaccharide specific humoral immunodeficiency. Immunological investigations showed compromised production of IgA, IgM, and IgG2. Isohaemagglutinins still were not detectable at the age of three years. Repeated vaccination with polyvalent pneumococcal polysaccharide vaccine did not result in production of specific antibodies. Two brothers showed clinical signs of ectodermal dysplasia. The elder brother died from pneumococcal sepsis at the age of 3 years. The younger brother suffers from chronic inflammatory gastrointestinal disease with ulcerations in all parts of the gastrointestinal system. Thus, a possible association between polysaccharide specific humoral immunodeficiency and ectodermal dysplasia may be considered.

Modified cow's milk formula with reduced renal acid load preventing incipient late metabolic acidosis in premature infants.

BACKGROUND: Premature infants receiving alimentation with cow's milk formulas are at a considerably high risk of developing incipient late metabolic acidosis, an early stage in the development of manifest late metabolic acidosis. Is it possible to reduce this risk by modification of the composition of a standard formula? METHODS: The mineral composition of a cow's milk preterm formula A was modified (formula B) with the aim of reducing the alimentary load to that of human milk. 160 premature infants were fed either mother's milk (n = 50) or the modified formula B (enriched with sodium and potassium) (n = 110), and their urine pH was tested twice a week. Randomly collected subgroups of infants were studied in detail for nutrient balances. The results were compared with earlier observations of 282 premature infants fed either mother's milk (n = 28) or the standard formula A (n = 254). RESULTS: Incipient late metabolic acidosis was observed in nine of 78 premature infants receiving mother's milk, 53 of 254 premature infants receiving the standard formula A, and only one of 110 premature infants fed the modified formula B. Net acid excretion was 0.58 mmol/kg/day in 11 premature infants receiving alimentation with the modified formula B compared with 1.73 mmol/kg/day in 23 premature infants fed formula A. This reduction was mainly due to an increased alkali excess (sodium + potassium-chloride) in intake and urine. CONCLUSIONS: Reduction of renal acid load with the modified formula B had a preventive effect on the rate of development of incipient late metabolic acidosis in premature infants.

Alkali therapy versus sodium chloride supplement in low birthweight infants with incipient late metabolic acidosis.

Two hundred and eighty-two patients with birthweights below 2.0 kg were routinely screened for spontaneous development of maximum renal acid stimulation (urine-pH < 5.4). Sixty episodes in 53 patients of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to oral therapy with 2 mmol/kg/day of either NaHCO3 or NaCl for 7 days. All 27 patients on NaHCO3 therapy, but only 15 from 26 patients on NaCl therapy, showed an increase in urine pH values, combined with a relatively high gain in body weight and a tendency to increased N-assimilation. Eleven patients on NaCl therapy showed persistent maximal renal acid stimulation on all 7 days with possibly lower weight gain and no clear change in N-assimilation. Thus, in patients with incipient late metabolic acidosis, NaCl therapy is not as beneficial as NaHCO3 therapy.

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula.

At present, not much is known about the absorption and metabolism of human milk (HM) oligosaccharides in term and preterm infants. We investigated the renal excretion of lactose and complex oligosaccharides in preterm infants fed HM (n = 9, mean actual body weight 2290 g) or a cow's milk-based infant formula (n = 9, mean actual body weight 2470 g). We found that the renal excretion of lactose in HM-fed infants was slightly lower than in formula-fed infants (14.0 +/- 7.4 versus 20.4 +/- 8.7 mg kg-1 day-1, mean +/- SD). The excretion of neutral sugars deriving from oligosaccharides was similar in HM-fed and formula-fed infants (3.8 +/- 2.1 versus 2.9 +/- 0.9 mg kg-1 day-1); the difference between means was not statistically significant. The separation and characterization of oligosaccharides by high-pH anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) and subsequent analysis by fast atom bombardment-mass spectrometry (FAB-MS) revealed a more complex pattern in HM-fed infants compared to the formula-fed group. Lactose-derived oligosaccharides characteristic for HM (e.g. lacto-N-tetraose, and lacto-N-fucopentaoses I and II) were excreted in HM-fed but not in formula-fed infants. These results indicate that nutrition has a significant impact on the oligosaccharide composition in urine of preterm infants.

[Neonatal hypoglycemia in congenital isolated aplasia of the adenohypophysis. A case report]. / Neonatale Hypoglykämie bei angeborener isolierter Aplasie der Adenohypophyse. Ein Fallbericht.

We report a female newborn with prolonged neonatal hypoglycaemia and vomiting. Endocrinologic studies demonstrated the absence of the anterior pituitary hormones ACTH, STH, LH, FSH, and PRL while TSH basal secretion as well as TSH stimulation were normal at the age of 2 months. Magnetic resonance imaging showed aplasia of the anterior pituitary and a nodular ectopic posterior lobe. Substitution with prednisone resulted in normalization of blood glucose values with clinical improvement of the patient. At the age of 8 months the patient was started on recombinant human growth hormone due to poor growth; with 10 months decrease of thyrotropin secretion resulted in additional thyroxine replacement therapy.

[Supplementation of premature infant nutrition with calcium and phosphor for improving mineral supply of premature and small-for-gestational age newborn infants]. / Anreicherung einer Frühgeborenenmilchnahrung mit Kalzium und Phosphor zur Verbesserung der Mineralstoffversorgung Früh- und Mangelgeborener.

A standard preterm formula was supplemented with calcium (Ca) and phosphorus (P) (F-CaP: Ca 87 mg/dl, P 43 mg/dl) and compared to the non-supplemented form (F: Ca 62 mg/dl, P 36 mg/dl). VLBW and small-for-gestational-age infants (n = 79) were included in the study which was performed to look for adverse effects and to decide about a reasonable start and duration of supplementation. In preterm infants with a birth weight lower than 1500 g and a body weight of more than 2000 g, the additional supplementation with Ca and P lead to a significant higher Ca- and P-retention without further load for the kidney. In addition, preterm infants with a body weight lower than 1500 g also had a better retention of Ca and P. Both, F-CaP and F lead to a high urinary excretion of phosphorus, a high renal net acid excretion and a relatively high activity of serum alkaline phosphatase. Anthropometric measurements did not reveal any evidence for an impaired caloric absorption due to an increased fecal fat excretion. Hypercalcemia or hyperphosphatermia was not seen. Hypercalciuria occurred in less than 5% of the samples studied. The results of this study indicate that a continuation of the supplementation with Ca and P is justified in VLBW infants with a body weight of more than 2000 g. There was no evidence for adverse effects of Ca and P supplementation in VLBW infants with a body weight lower than 1500 g, who might therefore also benefit from supplementation. Further studies are necessary to investigate unsatisfactory metabolic conditions of these children e.g. the high renal load.

Urinary excretion of aldosterone, arginine vasopressin and cortisol in premature infants with maximum renal acid stimulation.

Of 452 low-birth-weight infants who were routinely screened for maximum renal acid stimulation (MRAS) (urine pH < 5.4), 149 episodes of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to either a control group or treatment with NaHCO3 or NaCl (2 mmol/kg/day each) for 7 days. Urinary excretion of aldosterone-18-glucuronide (Aldo), arginine vasopressin (AVP) and cortisol was determined in timed urine samples. On day 1, patients with MRAS showed a tendency towards increased urinary excretion of Aldo compared with infants without MRAS. In patients who received alkali therapy, urinary excretion of Aldo, AVP and cortisol decreased or showed a trend to lower values from day 1 to day 7, whereas in patients with MRAS but no specific therapy, Aldo and AVP showed a tendency to increase. We concluded that persistent MRAS is not only characterized by a reduced rate of weight gain and a tendency to decreased nitrogen assimilation, but also increased secretion of Aldo and AVP.

The Haldane effect under different acid-base conditions in premature and adult humans.

The Haldane effect (HE) was investigated in human adults and prematures under normal metabolic acid-base conditions but at different levels of PCO2. Venous blood samples were equilibrated with low and high PCO2 in either O2 or N2. The change in plasma pH of oxygenated blood by deoxygenation did not differ between both groups. Thus, ontogenetic differences of human hemoglobin structure do not influence the net proton Haldane effect measured in terms of whole blood pH-changes. Since the present data quantitatively agree with those we reported earlier for rabbits, cats and dogs (Kiwull-Schöne et al., 1992), phylogenetic differences in hemoglobin structure of these mammalian species do not either seem to play a role in this respect. The influence of the Haldane effect on plasma pH has to be considered in blood-gas and acid-base analysis of samples with incomplete oxygenation. This is important for the indirect determination of PCO2 through pH by the equilibration method (Astrup and Schrøder, 1956), serving as reference method for determination of metabolic acid-base status and CO2 buffering capacity. Likewise, HE-correction is important for indirect estimation of metabolic acid-base status (BE and HCO-3st) from clinical routine PCO2- and pH-measurement. In spite of the vaste amount of literature on the Haldane effect in human blood, quantitative data for practical purpose are less available and still equivocal. By the present study, a strong inverse linear correlation between the HE-induced delta pH and 1g[HCO3-] could be shown over a wide range of acid-base changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Presence of re-appearance of BCR-ABL-positive cells years after allogeneic bone marrow transplantation for chronic-phase chronic myelogenous leukemia in patients in hematological remission.

Allogeneic bone marrow transplantation (BMT) is considered to be the only curative therapy for chronic myelogenous leukemia (CML). The cytogenetic marker of CML, the Philadelphia (Ph) chromosome, or the molecular alterations caused by the BCR-ABL gene fusion can be used to monitor the success of treatment. A sensitive two-step reverse-transcription polymerase chain reaction (RT-PCR) was done to score BCR-ABL-mRNA-positive leukemic cells in frozen bone marrow samples of 15 CML patients retrospectively. These patients, 4 females, 11 males, had undergone BMT during the first chronic phase after a preparative regimen consisting of total body irradiation (TBI) and cyclophosphamide; median age at BMT was 38 years (range 20-49 years). At the time of this study, 8 patients were in cytogenetic and/or clinical remission. Seven patients relapsed after BMT; all presented with Ph-chromosome-positive metaphases and BCR-ABL-positive cells at the time of relapse. In only 1 patient in hematologic remission was no positive PCR analysis obtained in the two samples tested. However, 5 patients have remained or became Ph-chromosome and/or PCR-positive after BMT without clinical symptoms of disease. In samples from another patient, transient presence of leukemic cells was observed only early after BMT. Clinically, these patients were relapse free at days 3,055, 2,581, 2,252, 1,846, 1,839, 1,747, and 1,173 after BMT, respectively. Based on these data, the presence of single BCR-ABL-positive cells > 1 year after BMT has no prognostic significance.

Increased renal net acid excretion in prematures below 1,600 g body weight compared with prematures and small-for-date newborns above 2,100 g on alimentation with a commercial preterm formula.

In 76 low birth weight infants with an actual body weight ranging from 1,210 to 2,540 g and fed a commercial preterm formula, urine samples were collected and blood acid base status was measured on day 38 (+/- 17, mean +/- SD) of life. Infants with an actual body weight below 1,600 g demonstrated a higher daily weight gain (22 +/- 3 vs. 14 +/- 5 g/kg/day), lower blood pCO2 (35.4 +/- 5.0 vs. 38.9 +/- 3.8 mm Hg), lower urine pH (5.8 +/- 0.5 vs. 6.5 +/- 0.3), higher renal net acid (1.86 +/- 0.38 vs. 1.28 +/- 0.55 mmol/kg/day) and higher phosphorus excretion (0.67 vs. 0.52 mmol/kg/day) than infants with an actual body weight above 2,100 g. Urinary ionogram data of these 2 groups of infants show that the increased renal net acid excretion of the smaller prematures is the result of a lower urinary excretion of sodium, potassium and chloride, due to a higher daily weight gain, probably a higher retention of these minerals, and a higher urinary phosphorus excretion probably due to an age-specific lower intestinal calcium absorption, and therefore a lower rate of calcium and phosphorus retention. Considering the low renal capacity for hydrogen ion excretion, very low birth weight infants still run a considerable risk for disturbances of acid base metabolism due to the high mean level of net acid excretion in nutrition with preterm formulas and an additional age-specific augmentation of renal acid load.

Decreased growth rate of low-birth-weight infants with prolonged maximum renal acid stimulation.

In a prospective randomized study, the urine pH of 170 premature and small-for-gestational-age (SGA) newborns was routinely screened to detect patients with spontaneously developing maximum renal acid stimulation, an obligatory early stage in the development of late metabolic acidosis. Nitrogen assimilation was evaluated from the ratio of urinary nitrogen excretion and intake. Forty-two premature infants and 10 SGA prematures and newborns after intensive care therapy with body weights greater than 1.5 kg and 25 prematures (including 7 SGA infants) with body weights less than 1.5 kg, spontaneously showed urine pH values below 5.4 on two consecutive days, suggesting maximum renal acid stimulation. These patients were randomly given either oral alkali therapy with sodium bicarbonate 2 mmol/kg/day or no therapy for a period of seven days. In both groups, urine pH was controlled daily. Patients in the control group without alkali therapy and with urine pH values less than 5.4 for seven days showed a significant decrease in weight gain and a tendency to decreased nitrogen assimilation. We assume that a regular check of urine pH in low-birth-weight infants is a useful non-invasive method of detecting patients in the early stages of development of late metabolic acidosis, i.e. in the stage of "incipient late metabolic acidosis". This would provide the possibility of starting early effective therapy and thereby reduce the mean duration of admission to neonatal wards.(ABSTRACT TRUNCATED AT 250 WORDS)

Low renal net acid excretion, high calciuria and biochemical signs of sodium deficiency in low-birth-weight infants fed a new low-phosphorus formula.

In 11 infants (birth weight greater than 1800 g) fed a new type of humanized formula with a low phosphorus (P) content (calcium (Ca) 11 mmol/l, P 7.2 mmol/l, sodium (Na) 8.3 mmol/l) biochemical parameters of blood, serum and urine were determined. In nine boys Ca and P balances were evaluated also. Renal net acid excretion was low (0.85 mmol/kg/day). Mean concentrations of P and Ca in urine were 0.34 mmol/kg/day (10.5 mg/kg/day) and 0.1 mmol/kg/day (4 mg/kg/day), respectively. In four infants, Ca concentration in urine was, however, greater than 0.15 mmol/kg/day) (6 mg/kg/day). In infants with birth weights greater than 1800 g fed the new, low-P formula, the low renal net acid excretion, the normal P and the high Ca concentrations in urine were comparable to term infants fed human milk. The high calciuria in several infants may be normal physiologic values. However, it remains to be established that the urinary solubility product of infants fed the new, low-P formula is in the same range as those for infants fed human milk. Unexpectedly, low urinary Na excretion (0.26 mmol/kg/day) and increased urinary excretion of aldosterone-18-glucuronide indicated biochemical evidence of Na deficiency secondary to low Na intake and a high weight gain. If the new, low-P formula is to be fed to infants with a birth weight as low as 1800 g. Na content should be higher than in mature human milk because of the often relatively higher weight gain.

Multiple minute marker chromosomes derived from Y identified by FISH in an intersexual infant.

Chromosomal analysis in a child with ambiguous sex showed mosaicism of at least two cell lines with one or more marker chromosomes or none at all. They were shown to be derived from the Y chromosome by fluorescent in situ hybridisation (FISH) using different DNA probes that cover parts of the long and the short arm.

Effect on renal net acid excretion of various mineral contents in three lots of a common pre-term formula.

Three common lots (A, B, C) of a common formula for pre-term infants, which contained unintended, high differences in mineral contents were fed consecutively in a neonatal unit. In each feeding period parameters of calcium-phosphorus and acid-base metabolism were determined prospectively. Infants fed lot C showed unexpectedly high renal net acid excretion. In order to discover the origin of this different renal net acid excretion, the urinary concentration of further electrolytes, sulfate, urea and organic acids were determined retrospectively in three randomly selected groups with 10 pre-term infants each. Infants fed lot C showed a higher renal net acid excretion (2.97 mmol/kg per day) than infants fed lot A (1.75 mmol/kg per day) or lot B (1.72 mmol/kg per day). Based on the data of mineral and nitrogen intake and the urinary values of all main ions and urea it is assumed that the increased renal acid load in infants fed lot C is due to the additive effect of different mineral concentrations resulting in a low "alkali excess" (Na + K - Cl) of lot C and a decreased protein assimilation. The production of infant formulas for prematures should be more closely monitored to avoid marked deviation of the mineral contents in individual lots from the concentrations shown on the label.

Renal handling of hydrogen ion excretion in relation to maturity indices in premature infants fed human milk.

In 40 premature infants fed human milk with an actual gestational age of 261 +/- 16 days and an actual body weight of 1.06-2.75 kg, 44 urine samples were collected, and blood acid-base status was measured on day 32 (+/- 16) of life. In the urine, the following results (mean +/- SD) were obtained: urine pH 6.05 +/- 0.65, titratable acidity 0.24 +/- 0.14 mmol/kg/day, ammonium 0.78 +/- 0.25 mmol/kg/day, net acid excretion 0.83 +/- 0.47 mmol/kg/day. There was no significant correlation between renal net acid or ammonium excretion and actual body weight. However, urine pH was positively correlated with body weight. Obviously, premature infants with an actual body weight below 1.5 kg need a higher stimulation of renal hydrogen ion secretion to excrete the same amount of ammonium than those with an actual body weight of about 2.5 kg. The limited renal acidification capacity of very low birth weight infants is a risk factor for the development of late metabolic acidosis.