摘要:

Preterm infants often show postural abnormalities, such as hyperextension of neck and trunk, which can interfere with motor and cognitive development. Little is, however, known on the pathophysiology of postural development in preterm infants. Therefore, we longitudinally studied the development of postural adjustments during reaching movements in 12 preterm infants between the (corrected) ages of 4 and 18 mo. Five infants showed minor neurological dysfunctions at 18 mo, such as a mild diffuse hypotonia, a mild hypertonia of the legs, or a mild asymmetry in posture and motility, and seven infants were neurologically normal. Each assessment consisted of a simultaneous recording of video-data and surface electromyograms of arm, neck, trunk, and leg muscles during reaching in various lying and sitting positions. Comparable data on postural development in ten fullterm infants were available. The preterm infants showed an excessive amount of postural activity during reaching movements at all ages studied. Moreover, the postural adjustments were temporally disorganized and could not be modulated with respect to the velocity of the arm movement and the initial sitting position. We hypothesized that the preterms' disability to modulate their postural adjustments might be due to a reduced capacity to learn from prior experience. In our small group the postural dysfunction were not related to the presence of hyperextension at early ages, to the neurological outcome at 18 mo, or to the lesions found on the neonatal brain ultrasound scans.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

After transient cerebral ischemia in fetal sheep, delayed disruptions in cerebral energetics are represented by a delayed increase in cortical impedance, a progressive decrease in the concentration of oxidized cytochrome oxidase as measured by near-infrared spectroscopy, and cortical seizures. Because the production of nitric oxide (NO), a potent mediator of neuronal death, is increased during this phase, the present study investigated whether inhibition of NO synthesis could ameliorate the delayed disruption in cerebral energetics. Eleven late gestation fetal sheep were subjected to 30 min of transient cerebral ischemiain utero. Two hours later, the treatment group (n= 5) received a continuous infusion ofNG-nitro-L-arginine, a competitive inhibitor of NO synthase, whereas the control group (n= 6) received PBS. Changes in concentration of oxidized cytochrome oxidase, cortical impedance, and electrocortical activity were observed for 3 d. A delayed increase in cortical impedance of similar magnitude and duration commenced at 14 ± 4 h in the control and at 15 ± 3 h in the treatment groups. The progressive decrease in oxidized cytochrome oxidase signal, by -2.2 ± 0.2 µmol/L in the control and -2.0 ± 0.4 µmol/L in the treatment group at 72 h postischemia, was similar in both groups. In both groups, delayed cortical seizures were indicated by intense low-frequency electrocortical activity. In the treatment group, duration of cortical seizures was increased and the intensity of the final electrocortical activity was more depressed (-19 ± 1 dBversus-10 ± 2 dB). The results indicate that after cerebral ischemia in fetal sheep, NO synthase inhibition does not ameliorate the delayed disruptions in cerebral energetics. However, the effect of NO synthase inhibition on delayed cortical seizures may improve our understanding of the role of NO during this phase.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Hepatocyte proliferation and differentiation occur simultaneously during late mammalian gestation. We hypothesized that regulation of hepatocyte growth and differentiation would be coordinated in late gestation fetal hepatocyte cultures such that proliferation would be most active in a population of less well-differentiated cells. Cultured fetal hepatocytes (embryonic d 19 and 21; E19 and E21) were studied using double staining immunofluorescent microscopy. Differentiation was assessed as staining for α-fetoprotein (AFP), three markers of enzymic differentiation (glucokinase [GK], phosphoenolpyruvate carboxykinase [PEPCK], and carbamoyl phosphate synthase [CPS]), and a hepatocyte cell-cell adhesion molecule (C-CAM). Proliferation was assessed using immunocytochemical detection of proliferating cell nuclear antigen (PCNA) or 5-bromo-2′-deoxy-uridine (BrdU) incorporation into DNA. Fetal hepatocyte cultures consisted of a heterogeneous population of cells, slightly more than half of which were proliferative under defined, growth factor-free conditions. These cultures were heterogeneous for AFP expression. There was no correlation between the expression of AFP and PCNA or AFP and S-phase entry (BrdU staining) during the first 48 h in culture. Similar results were obtained in staining for the enzymic differentiation markers and C-CAM. In addition, the differentiation status of cultured fetal hepatocytes was unrelated to a presumed indicator of mature growth regulation, mitogenic responsiveness to transforming growth factor α (TGFα), and hepatocyte growth factor (HGF). Finally, absence of any correlation between proliferation and differentiated phenotype was supported byin vivostudies using staining for PCNA, AFP, CPS, and PEPCK in liver sections. These results indicate that the developmental program governing differentiation of late gestation fetal rat hepatocytes is independent from mechanisms controlling proliferation.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Biotinidase deficiency is an autosomal recessive disorder of biotin metabolism that can lead to varying degrees of neurologic and cutaneous symptoms when untreated. Because this disorder meets the criteria for newborn screening, many states and countries perform this testing. Because newborn screening should result in complete ascertainment of mutations causing profound biotinidase deficiency (less than 10% of mean normal serum activity), we compared the mutations in a group of 59 children with profound biotinidase deficiency who were identified by newborn screening in the United States with 33 children ascertained by exhibiting symptoms. Of the 40 total mutations identified among the two populations, four mutations comprise 59% of the disease alleles studied. Two of these mutations occur in both populations, but in the symptomatic group at a significantly greater frequency. The other two common mutations occur only in the newborn screening group. Because two common mutations do not occur in the symptomatic population, it is possible that individuals with these mutations either develop mild or no symptoms if left untreated. However, inasmuch as biotin treatment is inexpensive and innocuous, it is still recommended that all children with profound biotinidase deficiency be treated.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Thrombocytopenia in the first days of life, in association with evidence of reduced megakaryocytopoiesis and platelet production at birth, is common in sick preterm babies. Thrombopoietin (Tpo) is the major regulator of platelet production in adults. However, these babies have low Tpo levels at birth, suggesting that the Tpo response to thrombocytopenia may be impaired. To test this hypothesis we1) measured Tpo levels,2) measured circulating megakaryocyte progenitors serially over the first 12 d of life in 13 preterm babies with early onset thrombocytopenia and in 14 control babies with evidence of normal megakaryocytopoiesis, and3) measured Tpo levels in thrombocytopenic children (n= 13). In control babies, platelet counts and progenitor numbers remained normal and Tpo levels were consistently low-d 1:160 ± 23 pg/mL (mean ± SEM), d 4/5: 154 ± 18 pg/mL and d 12: 150 ± 58 pg/mL. In thrombocytopenic babies, platelet counts and megakaryocyte progenitor numbers were significantly lower than controls at d 1: platelets 130 ± 14 × 109/Lversus255 ± 20 × 109/L (p< 0.001) and megakaryocyte progenitors 552versus3907 colonies/mL (mean,p< 0.001), and fell further to nadir on d 4/5: platelets 76 ± 6 × 109/Lversus259 ± 21 × 109/L (p< 0.001) and MK progenitors 479versus2742 colonies/mL (p< 0.05). Tpo levels were only slightly raised on d 1:247 ± 52 pg/mL (p= 0.24), but then rose sharply by d 4/5: 425 ± 75 pg/mL (p< 0.001). By d 12, platelet count, megakaryocyte progenitors and Tpo level (145 ± 29 pg/mL) had returned to control levels. Tpo levels at platelet nadir in thrombocytopenic babies were significantly lower than in thrombocytopenic children: mean 425versus1383 pg/mL (p< 0.001). These data show that Tpo is important in platelet homeostasis in preterm babies, with a close reciprocal relationship with platelet count and progenitor numbers during thrombocytopenia. However, the increase in Tpo levels seen in these babies was modest, despite significantly impaired megakaryocytopoiesis, and when compared with that seen in children with thrombocytopenia. This offers further evidence that preterm babies have an impaired Tpo response to thrombocytopenia and suggests that recombinant human Tpo may have a role in the prevention/treatment of preterm thrombocytopenia.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

To evaluate changes in autonomic nervous system controls in response to obstructive events in future victims of sudden infant death syndrome (SIDS), we studied the polysomnographic sleep recordings of 18 future SIDS infants and those of 36 matched control infants. A heart rate autoregressive power spectral analysis was performed preceding and after the obstructive apneas. The low-frequency to high-frequency power ratio was computed to evaluate sympathovagal balance. Future SIDS victims had significantly more obstructive apneas (p= 0.001) and mixed apneas (p= 0.005) than control infants. Obstructive events occurred mainly during rapid eye movement sleep in the two populations (84.5% in future SIDS victims and 95.8% in control infants;p= NS). Comparing heart rate power spectral analysis before and after obstructive apneas in rapid eye movement sleep, high-frequency power values were significantly lower and low-frequency to high-frequency power ratios higher in future SIDS victims than in control infants. Compared with preapnea values, low-frequency to high-frequency power ratios significantly decreased after obstructive apneas in control infants (p< 0.001) but not in the future SIDS victims. When the obstructive apneas were divided according to duration, the findings were seen mainly for long apneas. In conclusion, future SIDS victims were characterized by different autonomic status and responses to obstructive apneas during sleep. These findings could be relevant to mechanisms implicated in some cases of SIDS.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The main objective of the present study was to determine whether a structured, laboratory-based exercise task would modify the energy expenditure (EE) and the pattern of spontaneous physical activity (PA) of obese boys on the day of an exercise laboratory visit and on the following day. Fourteen 10- to 15-y-old moderately obese (36.6 ± 3.3% fat) boys volunteered. They each had three laboratory visits, 1 wk apart. In one visit, they performed a strenuous 50-min cycling task; in another, a 30-min medium-intensity cycling task; and in another (which served as placebo), they did not exercise. PA was monitored the day before (d 1), during (d 2), and after (d 3) each laboratory visit by use of a heart rate monitor and a 12-h recall interview. EE was calculated from minute-by-minute heart rate and each child's predetermined relationship between oxygen uptake and heart rate. EE and PA were analyzed from 1300 to 1900 h each day using 15-min intervals. EE tended to decrease (p< 0.087) in the afternoon of all d 2 compared with d 1, and it increased on d 3 after the medium-intensity exercise (p< 0.0005). EE during d 2 and 3 combined, compared with d 1, decreased after the high-intensity exercise (534.2versus564.3 kJ/h,p< 0.05). It increased after the medium-intensity exercise (561.8versus526.7 kJ/h,p= 0.052) and was not affected after the placebo visit (589.4versus574.3 kJ/h). Time spent outdoors was consistently reduced on the day of laboratory visit compared with the day before and after the visit, regardless of the contents of intervention In conclusion, a single laboratory visit is followed by a reduction in EE and PA on the day of intervention. However, its effect on EE the following day may be dose dependent: medium-intensity exercise induces an increase in EE, but high-intensity exercise causes a decrease in EE. One implication is that intervention by physical training should employ medium-intensity exercise to enhance the EE of obese boys.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Trifunctional protein (TFP) plays a significant role in the mitochondrial β-oxidation of long-chain fatty acids. Its deficiency impairs the energy generating function of this pathway and causes hypoketotic hypoglycemia once hepatic glycogen stores are depleted. A Reye-like syndrome, cardiomyopathy, and sudden death may follow. The diagnosis is based on demonstration of significantly decreased enzyme activity of at least two of the three involved enzymes in fibroblasts. The possibility of prospective diagnosis of TFP deficiency by newborn screening using tandem mass spectrometry (MS/MS) has not been evaluated. We report the postmortem diagnosis of a male newborn, who suffered sudden death at 2 wk of age, and his younger sister, who died of cardiomyopathy complicated by acute heart failure at the age of 6 mo, after she had acquired a common viral infection. Blood spots from the original newborn screening cards were the only remaining material from the patients. Analysis by MS/MS revealed acylcarnitine profiles consistent with either TFP or long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency. To prove the diagnosis, the α- and β-subunit genes coding for TFP were examined. The patients were compound heterozygous for a 4-bp-deletion and an a→g missense mutation, both in the same exon 3 donor consensus splice site. This is the first report of the diagnosis of TFP deficiency using blood spots obtained for newborn screening and suggests that TFP deficiency may be detectable by prospective newborn screening using MS/MS.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Near-infrared spectroscopy (NIRS) is a technique that is increasingly being used for the noninvasive measurement of cerebral blood volume (CBV) in newborn infants, but it has not been fully validated against established methods. These experiments in immature lambs (gestation 92 ± 1 d, mean ± SEM) compared CBV measured using NIRS-derived estimates of oxygenated Hb (n= 5) with CBV estimated with radiolabeled indicators (125I-labeled serum albumin and51Cr-labeled red blood cells,n= 10). Total brain CBV (mL/100 g tissue) measured using NIRS was 2.5 ± 0.2 compared with 2.5 ± 0.2 using radiolabels (NS). Regional tissue plasma, red blood cells, and whole blood volumes from radiolabels varied significantly (p≤ 0.05) throughout the brain. Whole blood volume (mL/100 g tissue) was largest in choroid plexus (16.2 ± 2.1) and least in white matter (0.7 ± 0.1) with a significant hierarchy evident among regions: choroid plexus > cerebellum > cortex > brain stem = midbrain > white matter. Regional plasma and red blood cell distributions were similar to whole blood, being highest in choroid plexus (13.0 ± 1.6 and 3.2 ± 0.9, respectively), and least in white matter (0.8 ± 0.1 and 0, respectively). These data from the immature lamb brain indicate that total CBV measured with NIRS is essentially identical with the volumes obtained using intravascular radiolabels. Among cerebral regions, white matter contributes little to the global blood volume measured with NIRS because its red blood cell content is very low.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Children with insulin-dependent diabetes mellitus (IDDM) suffer from a chronic autoimmune β cell destruction of unknown origin, maybe due to superantigens or retroviral endogenous genes. Recently, a novel endogenous retrovirus designated as IDDMK1,222 was proposed to encode for such a candidate autoimmune gene in type 1 diabetes. We therefore analyzed the expression of IDDMK1,222 genes in peripheral blood leukocytes and plasma from 55 healthy children and 55 diabetic children including 11 patients with acute disease onset. In our study we applied an improved quantitative and highly specific real-time PCR assay. In contrast to previous data obtained by conventional PCR, IDDMK1,222 gene expression did not differ between diabetic and nondiabetic individuals. For this reason, we propose that IDDMK1,222 is an ubiquitous endogenous retroviral element in the human genome but not a candidate autoimmune gene for IDDM, especially in childhood-onset disease. Real-time PCR proved to be a highly sensitive and specific method for detection and quantitation of very low amounts of mRNA and will thereby be useful regarding the special demands in pediatric studies dealing with very low amounts of specimen.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID