ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The a- and b-globin gene clusters are subject to several levels of regulation. They are expressed exclusively in the erythroid cells, only during defined periods of development and in a perfectly tuned way, assuring, at any stage of ontogeny, a correct balance in the availability of a- and b-globin chains for hemoglobin assembling. Such a tight control is dependent on regulatory regions of DNA located either in proximity or at great distances from the globin genes in a region characterized by the presence of several DNAse I hypersensitive sites and known as the Locus Control Region. All these sequences exert stimulatory, inhibitory or more complex activities by interacting with transcription factors that bridge these regions of DNA to the RNA polymerase machinery. Many of these factors have now been cloned and the corresponding mouse genes inactivated, shading new light on the metabolic pathways they control. It is increasingly recognized that such factors are organized into hierarchies according to the number of genes and circuits they regulate. Some genes such as GATA-1 and 2 are master regulators that act on large numbers of genes at early stage of differentiation whereas others, like EKLF, stand on the lowest step and control only single or limited number of genes at late stages of differentiation. We will review recent data gathered from expression studies in cell cultures, in transgenic or K.O. murine models as well as from a clinical settings. We will also discuss the development of novel theories on the regulation of the a- and b-globin genes and clusters.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Early adrenal insufficiency is associated with cardiopulmonary dysfunction in immature infants. Isolated cortisol levels and ACTH stimulation testing may not adequately show ontogeny of postnatal cortisol secretion nor identify at risk infants. Our objectives were 1) to determine postnatal urinary cortisol excretion rate (UCER) from birth to 14 d in immature baboons and 2) to evaluate the relation between UCER and cardiac performance. UCER was assessedvia6-h blocked urine collections from birth to 336 h of age in twenty-one 125-d gestation (term = 185 d) baboons. Urinary cortisol was measured by RIA. Cardiopulmonary parameters were averaged over the same time periods as urine collection. Serial two-dimensional echocardiograms were performed. After 24-h age, a subgroup (n= 8) received up to four doses (0.5–1.0 mg/kg each) of hydrocortisone for refractory hypotension. UCER significantly increased from 0 to 6 h through 66 to 72 h age for non-cortisol-treated infants. Significantly reduced UCER patterns between birth and 24 h were found for animals subsequently requiring cortisol treatment. Cortisol-treated infants had lower mean blood pressure, worse metabolic acidosis, increased fluid needs, and impaired left ventricular function between 12 and 48 h of age. No group differences were found in gas exchange or ventilator support. We conclude that adrenal cortisol secretion significantly improves over the initial 72 h of life in the 125-d immature baboon. Failure to increase UCER after 12–24 h of life correlated with poor cardiovascular function that improved with hydrocortisone therapy. Adrenal hypofunction in the immature baboon is similar to the very preterm human and could serve as a model for future postnatal investigations.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Clinical depression, diagnosed in 5–15% of women during pregnancy, increases the risk of negative pregnancy outcomes including an increased incidence of low birth weight newborns and preterm delivery. Fluoxetine, a selective serotonin reuptake inhibitor, is often prescribed to treat depression due to its efficacy, high margin of safety, and mild side effects. However, fluoxetine initially increases plasma serotonin concentration, and serotonin causes uterine vasoconstriction in sheep, which could result in fetal hypoxemia. To assess fetal fluoxetine effects, late-gestation pregnant sheep were surgically prepared for the measurement of blood gases, heart rate, blood pressure, and uterine artery blood flow (n= 29). Ewes received a 70-mg bolus i.v. infusion of fluoxetine over 2 min in 10 mL of sterile water followed by continuous infusion at a rate of 100 &mgr;g/min for 8 d (n= 14), or continuous infusion of sterile water (n= 15). Transient decreases in uterine artery blood flow, fetal Po2, and oxygen saturation were observed within the first 15 min after fluoxetine exposure, which did not return to normal values by 24 h. Fetal pH decreased and Pco2increased over the first 4 h with a return to normal by 24 h. However, there were no differences in uterine artery blood flow, blood gas status, or cardiovascular measures between the control and fluoxetine group over the rest of the 8-d infusion period. Thus, fluoxetine exposure during pregnancy has transient effects on fetal status that may be of developmental consequence if they occur repetitively.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and &ggr;-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n= 7), paroxetine (n= 11), sertraline (n= 4)]; 16 infants exposed to SSRIs and clonazepam (SE+) [paroxetine (n= 14), fluoxetine (n= 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups—[mean (range)] SE:SE+ 183 (31–281):141 (54–282) d (p> 0.05). Infants exposed to SE and SE+ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition, pharmacologic factors and the developmental course remain to be studied.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Auditory neural responses to acoustic stimuli of different rates were studied by analyzing changes in brainstem auditory evoked responses (BAER) with increasing repetition rate of clicks, or rate-dependent changes, in 62 very preterm babies (gestation 24–32 wk). None had perinatal asphyxia or major complications at the time of testing (37–42 wk postconceptional age) to exclude their possible effects on the recorded BAER. As the rate of clicks was increased from 21/s to 51/s and 91/s, I–V interpeak interval in these babies increased similarly to that in normal term neonates. The rate-dependent change decreased significantly in I–III interval, but increased significantly in III–V intervals and III–V/I–III interval ratio (allp< 0.01). At all three rates of clicks, the I–V interval, the most commonly used BAER variable, tended to increase slightly but did not differ significantly from the term neonates. The I–III interval decreased significantly at higher click rates (ANOVAp< 0.05 at 51/s and < 0.001 at 91/s), whereas the III–V interval and III–V/I–III interval ratio increased significantly at all 21/s, 51/s, and particularly 91/s (p< 0.01–0.001). No abnormalities were found in wave V amplitude at any rates. These results suggest that very preterm babies have an advanced peripheral development of the brainstem auditory pathway but a retarded central development or central impairment. A nearly normal I–V interval does not exclude a possible abnormality in its subcomponents (I–III and III–V intervals). In babies who have a normal BAER at a conventionally used low rate of clicks, we cannot exclude an abnormal BAER at higher rates.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Many attempts have been made to obtain safe and effective analgesia in newborns. Oral glucose-water has been found to have analgesic properties in neonates. We investigated whether other sensory stimulation added to oral glucose provided more effective analgesia than oral glucose alone. In a randomized prospective double-blind trial, we studied 120 term newborns during heel prick. The babies were divided randomly into six groups of 20, and each group was treated with a different procedure during heel prick:A) control;B) 1 mL 33% oral glucose given 2 min before the heel prick;C) sucking;D) 1 mL 33% oral glucose plus sucking;E) multisensory stimulation including 1 mL 33% oral glucose (sensorial saturation);F) multisensory stimulation without oral glucose. Sensorial saturation consisted in massage, voice, eye contact, and perfume smelling during heel prick. Each heel prick was filmed and assigned a point score according to the Douleur Aiguë du Nouveau-né (DAN) neonatal acute pain scale. Camera recording began 30 s before the heel prick, so it was impossible for the scorers to distinguish procedure A (control) from B (glucose given 2 min before), C (sucking water) from D (sucking glucose), and E (multisensory stimulation and glucose) from F (multisensory stimulation and water) from the video. Procedure E (multisensory stimulation and glucose) was found to be the most effective procedure, and the analgesia was even more effective than that produced by procedure D (sucking glucose). We conclude that sensorial saturation is an effective analgesic technique that potentiates the analgesic effect of oral sugar. It can be used for minor painful procedures on newborns.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID