摘要:

Twenty-two French patients with early treated phenylketonuria (PKU) off diet (no reduced phenylalanine, Phe) since their 5th birthday, 23 German patients on diet (reduced Phe), and 21 healthy control subjects from childhood to adulthood matched for age, sex, and IQ were investigated for visuomotor reaction time, sustained attention, and visual stimulus scanning. Determinations were made whether1) the three groups showed different developmental trends in their reaction times,2)the threshold of a Phe blood level of 360 μmol/L formulated in recent recommendations can be regarded as safe,3)test performances are related to the quality of dietary control in the same way for all age groups, and4) long-term elevated Phe levels result in aggravating effects of increasing differences between patients on and off diet and healthy controls. Results revealed that developmental trends were similar in all treatment groups. Only children with a mean Phe level below 360 μmol/L performed as well as control subjects. Differences between treatment groups decreased in adulthood, and no aggravating effect could be observed. Mean performance of patients with mild PKU off diet was in the same range as performance of patients with classical or mild PKU on diet, calling into question the benefit of treating these patients. It is concluded that it is preferably safer to maintain Phe blood levels below 360 μmol/L at least during the first 10 y of life.Abbreviations: DPE,dot pattern exercise;FMSE,finger motor speed exercise;LPE,letter pattern exercise;Phe,phenylalanine;PKU,phenylketonuria;SDS,standard deviation score;SDST,standard deviation of series time;ST,series time;SVAT,Sonneville visual attention task;WAIS-R,Wechsler Adult Intelligence Scale-Revised;WISC-R,Wechsler Intelligence Scale for Children-Revised

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Thyroid hormone status was assessed in 132 children with congenital heart defects undergoing cardiac surgery (median age 3.1 y; range 2 d to 16.2 y). Plasma TSH, thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyroglobulin (Tg), and urinary iodine excretion were measured before and every other day after cardiac surgery (d 1-21). After surgery we observed strikingly low plasma concentrations of TSH (0.4 mU/L; 0.2-1.3), T3(0.6 nmol/L; 0.3-1.2), T4(48.9 nmol/L; 12.9-82.4), fT4(12.9 pmol/L; 5.1-19.3), and Tg (9.4 μg/L; 1.5-20.6), whereas rT3plasma concentrations increased (0.13 pmol/L; 0.05-0.3;n= 40). The maximal postoperative changes of TSH and rT3preceded changes of T3, T4, fT4, and Tg. Postoperative urinary iodine excretion increased significantly (n= 109). Thyroid hormone plasma concentrations were lowest after cardiopulmonary bypass operations and in patients treated with dopamine. In patients with postoperative T3plasma concentrations less than 0.6 nmol/L (n= 52) the period of mechanical ventilation and intensive care treatment was significantly prolonged. Furthermore, the cumulative doses of inotropic and vasoactive catecholamines and furosemide were significantly higher in this patient group. Our results demonstrate transient secondary hypothyroidism in children after cardiac surgery that may contribute to postoperative cardiac and respiratory dysfunction and may delay recovery. Possible benefits of thyroid hormone replacement therapy need to be thoroughly examined.Abbreviations: T4,thyroxine;fT4,free thyroxine;T3,triiodothyronine;rT3,reverse triiodothyronine;Tg,thyroglobulin

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.Abbreviations: PTHrP,PTH-related protein;PCR,polymerase chain reaction;HMEC,human mammary epithelial cells

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Data are scarce regarding mineral bioavailability from human milk in older infants who may also be receiving solid foods (beikost). We measured the absorption of Ca, Zn, and Fe in 14 healthy, nonanemic 5-7-mo-old breast-fed infants whose mothers' milk was extrinsically labeled with stable isotopes(44Ca,70Zn, and58Fe) of these minerals. In addition, Ca and Zn stable isotopes (46Ca and67Zn) were administered i.v., and a second isotope of Fe (57Fe) was given orally without food as a non-meal dose. Subjects were not receiving any artificial infant formula or cow's milk, but most (10/14) were receiving beikost. Ca and Zn absorption was calculated using the urinary excretion of the isotopes during the 24 h after dosing (Ca) or their urinary ratio 72 h after dosing (Zn). Fe absorption was calculated using the red blood cell incorporation at 14 d. Fe absorption averaged 20.7 ± 14.8% from the58Fe given with human milk(geometric mean, 14.8%) and 17.7 ± 15.1% (geometric mean, 11.0%) from the57Fe non-meal dose. Ca absorption averaged 61.3 ± 22.7% and Zn absorption (n= 10) averaged 49.5 ± 18.5%. Absorption of Fe (natural logarithm) from the non-meal Fe dose (57Fe) but not from the human milk (58Fe) was significantly negatively correlated to serum ferritin (r= -0.70,p= 0.007versus r= -0.35,p= 0.24). At the intake levels in this study, total daily Fe, Ca, and Zn intakes from beikost were not significantly correlated to their fractional absorption from breast milk, but Fe intake from beikost was significantly negatively correlated to absorption of Fe from the non-meal dose(r= -0.61,p= 0.021). We conclude that minerals are well absorbed from human milk in older infants after the introduction of beikost to the diet.Abbreviations: RBC,red blood cell;IDPM,i.v. distribution pool mass

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To quantitate glutamine kinetics in premature infants and determine whether glutamine affects leucine metabolism, 11 very low birth weight (<1250 g) neonates received 4-h i.v. infusions of L-[2H3]leucine and L-[13C5]glutamine, along with orogastric infusion of L-[1-13C]leucine and L-[1-13C]glutamine on the 10th d of life and in the fed state. Patients were receiving parenteral nutrition and were randomized to receive either hypocaloric, enteral preterm formula alone(controls;n= 5), or glutamine (0.2 g·kg-1·d-1on the day of the study) supplemented formula (GLN;n= 6). The rates of appearance (Ra) of leucine and glutamine, and their rates of splanchnic extraction were determined from isotopic enrichments in plasma at steady state. Leucine release from protein breakdown did not differ between groups (123 ± 51versus162 ± 94 μmol·kg-1h-1in the controls and GLN group, respectively). Glutaminede novosynthesis accounted for >80% of overall glutamineRa, and was similar in both groups (626 ± 177versus525 ± 86μmol·kg-1·h-1; NS); 46 ± 16% and 53± 31% of the enteral glutamine underwent first-pass splanchnic extraction in the controls and GLN group, respectively. These findings indicate that the pathways of glutaminede novosynthesis and glutamine utilization in the splanchnic bed are functional in very low birth weight humans by the 10th d of life. Glutamine supplementation provided at low doses on a hypocaloric regimen results in no apparent differences in flux of glutamine or leucine.Abbreviations: VLBW,very low birth weight;PN,parenteral nutrition;GCMS,gas chromatography-mass spectrometry;OG,orogastric;KIC,α-ketoisocaproic acid;Ra,rate of appearance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Bone turnover, collagen metabolism, and bone mineral status were investigated in 59 patients with cystic fibrosis and in 72 sex- and age-matched control subjects. In all patients and control subjects serum concentrations of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen(PIIINP), and cross-linked carboxy-terminal telopeptide of type I collagen(ICTP), and urinary values of cross-linkedN-telopeptides of type I collagen (NTX), as well as total body bone mineral content (TBBM) were measured. Higher ICTP (μg/L) and NTX (bone collagen equivalent/urinary creatinine (nmol/mmol) values were found in prepubertal, pubertal, and young adult patients than in control subjects (ICTP: 15.4 ± 2.1 and 13.2± 1.8,p< 0.001; 23.3 ± 5.3 and 20.1 ± 4.1,p< 0.02; 4.8 ± 1.1 and 4.0 ± 1.0,p< 0.05, respectively; NTX: 1047.5 ± 528.6 and 227.8 ± 71.8,p< 0.01; 997.8 ± 391.7 and 376.3 ± 91.0,p< 0.01; 993.2 ± 398.0 and 73.9 ± 28.5,p< 0.01, respectively). Lower OC and PICP levels (μg/L) were showed in pubertal patients in comparison with control subjects (OC: 20.2± 12.3 and 39.0 ± 15.1,p< 0.01; PICP: 305.8± 130.4 and 436.2 ± 110.1,p< 0.02, respectively). Lower OC and higher PIIINP levels (μg/L) were found in young adult patients than in control subjects (OC: 4.4 ± 3.0 and 7.0 ± 3.1,p< 0.05; PIIINP: 4.8 ± 1.1 and 3.1 ± 1.0,p< 0.001, respectively). TBBM (zscore) was reduced in prepubertal, pubertal, and young adult patients (-0.8 ± 0.4, -1.0± 0.4, -1.1 ± 0.5, respectively). Patients with cystic fibrosis have bone demineralization and imbalance between bone formation and degradation.PIIINP,amino-terminal propeptide of type III procollagen;BMI,body mass index;PICP,carboxy-terminal propeptide of type I procollagen;ICTP,cross-linked carboxy-terminal telopeptide of type I collagen;NTX,cross-linkedN-telopeptides of type I collagen;CF,cystic fibrosis;OC,osteocalcin;TBBM,total body bone mineral content;BCE,bone collagen equivalent

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Kynurenic acid (KYNA) is a tryptophan metabolite and represents the only known endogenous compound acting as an antagonist to excitatory amino acid receptors in the mammalian CNS. Blocking of these receptors in CNS by KYNA affects cardiac function. As it is not known whether human heart is able to synthesize this neuromodulatory amino acid, we investigated the biosynthesizing enzyme of kynurenine aminotransferase (KAT) in the human heart and compared the activity with that of the human brain. The activities of heart and brain KATs were assayed by the conversion of L-kynurenine (L-KYN) to KYNA and quantitated by HPLC with fluorescence detection. Using either pyruvate or 2-oxoglutarate as cosubstrates, heart KAT was found to have a shallow pH optimum between 8 and 9. Highest heart KAT activity was seen in the presence of 2-oxoglutarate, followed by pyruvate, 2-oxoadipate, and 2-oxoisocaproate. Kinetic analyses, performed at pH 8.5, and using various concentrations of L-KYN (from 0.125 to 22.8 mM) in the presence of 2-oxoglutarate (1 and 5 mM) or pyruvate (5 mM) revealed apparentKmvalues in the millimolar range, for L-KYN 1.5, 27, and 20 mM, respectively. Heart KAT activities were compared with those in human brain KAT I and KAT II showing different pH optima 7.4 and 9.6, respectively. In contrast to brain KAT I, heart KAT activity was not inhibited by an excess of 2 mM L-tryptophan, L-glutamine, or L-phenylalanine at pH 9.6, as well as at pH 8 or 7.4. Our study demonstrates that human heart is capable of synthesizing KYNA from low concentrations of L-KYN selectively. A shallow pH optimum of KAT activity,i.e.between 8.0 and 9.0, pronounced 2-oxoacid specificity, and a lack of sensitivity to inhibition by L-glutamine, L-phenylalanine, and L-tryptophan indicate that the heart KAT system displays enzymatic characteristics different from those of human brain KAT I or KAT II. Fluctuation of L-KYN and 2-oxoacid levels may markedly influence the KYNA synthesis and subsequent KYNA effect on cardiac activity. KYNA synthesis in the human heart suggests a neurophysiologic role. Our studies form the basis for purification and further characterization of KAT protein in human heart as well as for physiologic studies.Abbreviations: KYNA,kynurenic acid;KAT,kynurenine aminotransferase [f]L-KYN, L-kynurenine;NMDA,N-methyl-D-aspartate;AMPA,α-amino-3-hydroxy-5-methyl-4-isoxazole propionate;AMP,2 amino-2-methyl-1-propanol;EAA,excitatory amino acid

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Opiates are widely used as obstetrical analgesics during pregnancy and, as such, their interactions with the fetal endocrine system may have important consequences. In this study, the effects of morphine administration to fetal sheepin uteroon fetal plasma immunoreactive (ir)-ACTH and ir-cortisol were examined. At the lowest dose administered (0.6 mg/h, i.v.) morphine reduced, although not significantly, plasma ir-cortisol levels. A dose-dependent stimulation of cortisol release was observed with higher doses of morphine. Doses of 2.5 and 5.0 mg/h morphine resulted in a significant increase in ir-cortisol with a change from control levels equal to 9.6± 1.1 ng/mL (p= 0.03) and 17.6 ± 5.1 ng/mL(p= 0.03), respectively. This increase in plasma ir-cortisol was associated with a significant increase in ir-ACTH (111.8 ± 23.2 pg/mLversus42.8 ± 5.1 pg/mL;p= 0.02) that was naloxone-reversible. These effects of morphine were observed in fetal lambs only >125 d of gestation, suggesting a maturation of functional opioid receptors in the ovine fetal hypothalamic-pituitary-adrenal axis after this time.Abbreviations: CRF,corticotropin-releasing factor;HPA,hypothalamic-pituitary-adrenal;ir,immunoreactive

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We hypothesized that treatment of very low birth weight premature infants with r-HuEPO would increase erythrocyte incorporation and gastrointestinal absorption of iron. Infants with birth weights ≤1.25 kg and gestational ages <31 wk were randomized to receive 6 wk of 500 U of r-HuEPO/kg/wk (epo group,n= 7) or placebo (placebo group,n= 7). All infants received daily enteral supplementation with 6 mg of elemental iron per kg. An enteral test dose of a stable iron isotope,58Fe, was administered after the 1st (“early dosing”) and 4th (“late dosing”) wk of treatment. Mean (±SD) erythrocyte incorporation of the dose of58Fe administered determined 2 wk after early dosing was significantly greater in the epo group compared with the placebo group (4.4%± 1.6versus2.0 ± 1.4%,p= 0.013). In contrast, after late58Fe dosing, there was no difference between groups in incorporation (3.8 ± 1.6%versus5.5 ± 2.7%). Within the epo group, percentage erythrocyte incorporation of58Fe did not differ between early and late dosing, whereas in the placebo group it increased 3-fold (p< 0.01). Percentage absorption of58Fe was not different between the epo and placebo groups after both early dosing (30 ± 22%versus34 ± 8%) and late dosing (32 ± 9%versus31 ± 6%). Absorption of nonlabeled elemental iron and58Fe were significantly correlated with one another. The percentage of the absorbed58Fe dose incorporated into Hb was not different between groups. We conclude that, although erythropoietin treatment stimulates erythrocyte iron incorporation in premature infants, it has no effect on iron absorption at the r-HuEPO dose studied.Abbreviations: epo,erythropoietin;r-HuEPO,recombinant human erythropoietin;IR,abundance isotope ratio

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The sheep is a useful model to study fetal and newborn physiology including perinatal erythropoiesis and red cell kinetics. A practical, economical method for measuring red cell survival (RCS) in sheep would be very valuable. However,51Cr is unsatisfactory, and suitable alternatives have not been published. In the course of investigating [14C]cyanate as a label for sheep red cells, we observed continued covalent labeling over 24 hin vivothat was great enough to introduce a substantial artifact into two commonly used parameters of RCS: posttransfusion recovery(PTR24) and time to 50% decrease (T50) when referenced to time zero. In a simulation ofin vivoconditions, the amount of14C bound to Hb increased 26 ± 6% (mean ± 1 SD,n= 11) over 24 h. To investigate the mechanism of the increasing14C bound, acid-acetone extraction, molecular sieve chromatography, and density gradient separation were used separately or in combination to quantitate intracellular free14C and14C covalently bound to intracellular proteins. Free14C decreased as protein-bound[14C]cyanate increased. These studies provide evidence that covalent binding of [14C]cyanate to intracellular Hb continuesin vivofor the first 24 h and that the source of the increase is intracellular free[14C]cyanate. We conclude that1) PTR24cannot be accurately determined by [14C]cyanate unless labeled red cells are incubated before infusion to allow the cyanate reaction to approach completion and2) RCS by [14C]cyanate should be referenced to blood concentrations at 24 h.Abbreviations: RCV,red cell volume;RCS,red cell survival;PTR24,posttransfusion recovery at 24 h;T50,time to decline 50% from reference value

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID