Biomedical subjects

J D DeCristofaro

Publications and source records attributed to J D DeCristofaro.

12 recordsLinked to original sources

PubMed2000

Prediction of postdischarge complications by predischarge event recordings in infants with apnea of prematurity.

OBJECTIVE: To determine whether predischarge event recording (PDER) can accurately identify preterm infants with resolving apnea of prematurity (AOP) at risk for postdischarge complications. DESIGN: PDER was performed on infants with resolving AOP on caffeine, ready for discharge. The outcome of infants with normal recordings was compared with that of infants with abnormal recordings. Follow-up data were obtained for outcome. RESULTS: Of the 106 infants, 74 had a normal PDER and 32 had an abnormal PDER (apneas lasting for > 20 seconds and/or a heart rate of < 80 beats per minute for > 5 seconds). Birth weight, gestational age at birth, length of stay, discharge weight, and duration of caffeine treatment after discharge were no different between groups. None of the normal PDER infants (0 of 74) had postdischarge complications, whereas 4 of 32 infants with an abnormal PDER had complications (p < 0.05, power = 0.7). The positive predictive value of a normal PDER and no postdischarge complications was 100%. The positive predictive value of an abnormal PDER and an adverse outcome was 12.5%. CONCLUSION: Normal PDER accurately identifies infants at low risk for an adverse outcome.

Apnea↗

PubMed2000

Effect of prenatal steroids on potassium balance in extremely low birth weight neonates.

OBJECTIVE: Potassium is the most abundant intracellular cation and plays an important role in a variety of cell functions. Potassium homeostasis and regulation are important aspects of fluid and electrolyte homeostasis in extremely low birth weight (ELBW) infants. Because prenatal steroid (PNS) treatment promotes maturation of many epithelial cell systems, we sought to determine whether PNS affects potassium homeostasis in ELBW infants (<1000 g) during the first week of life. METHOD: Serum potassium (SK) concentration, potassium intake and output, and renal clearance were collected prospectively each day during the first week of life. Infants whose mothers received a full course of steroids before delivery (PNS group: n = 16) were compared with those infants whose mothers did not receive steroids (nonsteroid group [NSG]: n = 14). The decision to treat with PNS was made entirely by the obstetric staff in a nonrandomized manner. Potassium intake and excretion and serum and urine electrolytes were measured every 12 hours, and urine output was monitored every 2 to 3 hours. Hyperkalemia was defined as SK >6. 5 mmol/L in a nonhemolyzed sample on at least 1 measurement from a central line. RESULTS: There were no significant differences between the groups in gestational age, Apgar score, and birth weight. SK increased initially after birth in the absence of exogenous K intake in all infants, then subsequently decreased and stabilized by day 4 of life. The peak SK was significantly lower in the PNS group than in the NSG group (5.2 +/-.2 mmol/L vs 6.2 +/-.4 mmol/L). Moreover, the peak SK was higher than 6.5 mmol/L in 70% of the NSG infants and in none of the PNS group. Hyperkalemia occurred in the NSG infants within the first 2 days when urine output was significantly lower than in PNS infants. SK peaked in the absence of potassium intake with similar potassium excretion in both groups. PNS infants had similar cumulative potassium intake with a lower cumulative potassium excretion than did NSG infants. PNS infants had a significantly less negative potassium balance than did NSG infants by day 7 of life (-1.0 mmol/kg vs -7.0 mmol/kg). There was no statistical difference in the daily serum creatinine levels, fractional excretion of potassium, and in the daily creatinine clearance between the 2 groups. CONCLUSION: We conclude that treatment with PNS prevents the nonoliguric hyperkalemia known to occur in ELBW neonates. We speculate that PNS induces upregulation of cell membrane sodium, potassium-adenosinetriphosphatase activity in the fetus. The differences in negative potassium balance may be accounted for by stabilization of cell membranes that may result in a decrease in potassium shift from intracellular to extracellular compartments.

Betamethasone↗

PubMed1999

Effects of prenatal steroids on water and sodium homeostasis in extremely low birth weight neonates.

OBJECTIVE: We sought to determine if prenatal steroid (PNS) treatment affects water and sodium (Na) balance in extremely low birth weight infants (<1000 g). METHODS: PNS treatment enhances lung maturation in preterm infants and induces maturation of renal tubular function and adenylate cyclase activity in animals. We compared water and Na homeostasis for the first week of life in those infants whose mothers received steroids before delivery (PNS: n = 16) to those who did not (nonsteroid group [NSG]: n = 14). The data were collected prospectively, but PNS treatment was not given in a randomized manner. Fluids were initiated at 100 to 125 mL/kg/d and adjusted every 8 to 12 hours to allow a daily weight loss of </=4% of birth weight and to maintain normal serum electrolytes. Weight, serum and urine electrolytes, and urine output were frequently measured and fluid intake was adjusted by increasing the amount of free water to achieve these goals. RESULTS: When using our fluid management protocol, the percent weight loss in both groups was equivalent during each of the 7 days (15% PNS vs 17% NSG maximum loss) as well as the cumulative urine output at 1 week of age (663 mL/kg/wk PNS vs 681 mL/kg/wk NSG). PNS infants had a higher urine output on the first 2 days of life and a lower daily fluid intake for the first week. PNS infants also had significantly less insensible water loss for each of the first 4 days of life. The PNS group had a significantly lower mean peak serum Na of 138 +/- 1 mmol/L vs 144 +/- 2 mmol/L and none had a peak serum Na >150 mmol/L compared with 36% of the NSG infants. PNS infants had a higher cumulative Na excretion at day 2 of life (10 +/- 2 mmol/kg vs 6 +/- 1 mmol/kg) but a less negative cumulative Na balance at 1 week (-10 mmol/kg vs -14 mmol/kg). CONCLUSION: PNS treatment was associated with lower estimated insensible water loss, a decreased incidence of hypernatremia, and an earlier diuresis and natriuresis in extremely low birth weight neonates. We speculate that PNS effects these changes through enhancement of epithelial cell maturation improving skin barrier function. PNS treatment may also enhance lung Na, K-ATPase activity leading to an earlier postnatal reabsorption of fetal lung fluid increasing extracellular volume expansion to help prevent hypernatremia.

Betamethasone↗

PubMed1998

Novel transcriptional mechanisms are involved in regulating preproenkephalin gene expression in vivo.

For the dissection of the temporal and spatial patterns of cell- and tissue-specific gene expression an understanding of the contributing regulating mechanisms is required. We now confirm that there are novel mechanisms regulating preproenkephalin gene expression in basal as well as cholinergic agonist treated rats. Moreover, we demonstrate that these novel transcriptional mechanisms are consistent with RNA intragenic elongation pausing, alternate promoter usage, and small sense and antisense RNA transcription from the preproenkephalin gene locus. We report that while basal striatal and olfactory bulb proenkephalin RNA transcripts are initiated from the "normal" proximal promoter, in cerebellum de novo RNA transcription appears to be initiated from the distal so-called "germ-cell" promoter. Furthermore, "normally" initiated olfactory bulb proenkephalin RNA transcripts appear to be down-regulated by the time the RNA polymerase II complex reaches the first preproenkephalin intron, in a way that is consistent with RNA elongation pausing. As the pattern of small sense and antisense transcripts found associated with this gene's expression is tissue-specific, we suggest that they may also play a role in regulating gene expression. The understanding of this gene's regulation should have widespread importance, not only to those interested in opioid gene expression, but also to those interested in gene regulation, in general.

Adrenal Medulla↗

PubMed1994

Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo.

The clinical benefit of transplantation therapies utilizing genetically modified cells could be enhanced if expression of engineered genes was regulated by clinically useful pharmacological agents. Toward this end, we examined pharmacologic effects on the expression of hybrid gene constructs transfected into primary rat striatal astrocytes. These astrocytes are known to express receptors for the neurotransmitter dopamine (DA). In vitro, we found that expression of a transiently transfected human ppEnk promoter-driven chloramphenicol acetyltransferase (CAT) reporter construct was induced by DAergic agonists, as much as 20-fold. This induction was blocked by a DA receptor antagonist. The same concentration of DA also increased the endogenous rat ppEnk mRNA, by > 2-fold. In vivo, regulation of CAT expression by DA was tested by implanting the genetically modified astrocytes into the normal striatum and the contralateral striatum which had > 95% DA depletion induced by a previous 6-hydroxy-DA lesion of the substantia nigra. As hypothesized on the basis of the in vitro data, CAT activity on the lesioned side, where the stimulating effect of endogenous DA was lacking, was 30% lower than on the control side where the normal DA content was present. The data suggest that control of the enkephalin gene in astrocytes may involve second messenger pathways activated by DA receptors. Moreover, the evidence that clinically applicable drugs can regulate inducible genes introduced into the brain by astrocyte implantation is of potential importance in development of therapeutic strategies.

Animals↗

PubMed1994

Neonatal stress: effects of hypoglycemia and hypoxia on adrenal tyrosine hydroxylase gene expression.

Catecholamines (CA) are released from and resynthesized in the adrenal medulla in response to stress. In the mature animal, stimulus-secretion-synthesis coupling occurs through transsynaptic (neuronal) activity. In contrast, in the immature animal, before functional adrenal innervation, certain stressors (hypoglycemia and glycopenia) do not result in CA release. Additionally, it is not known whether release and biosynthesis remain coupled in the neonate as they are in the adult. Therefore, to evaluate whether neonatal stressors can induce CA biosynthesis at the genomic level "directly" before function adrenal innervation, we studied the expression of the tyrosine hydroxylase (TH) gene, the rate-limiting enzyme in CA biosynthesis. Newborn rat pups were made either hypoxic, hypoglycemic, or cellularly glycopenic (2-deoxyglucose). Neither hypoxic stress nor insulin-induced hypoglycemic stress altered steady state levels of TH mRNA in the neonate. However, cellular glycopenia resulted in a significant 2-fold rise in TH mRNA levels (p < 0.05). As expected, each of these stressors increased TH mRNA levels in the mature adult rat. Thus, neonatal hypoxia and hypoglycemia appear to require intact neurogenic impulse activity, whereas cellular glycopenia may "directly" induce TH RNA, perhaps through hormonal mechanisms. This developmental model allows for the analysis of mechanisms governing adrenal CA release separate from those governing biosynthesis at the level of TH RNA. Acute neonatal hypoxic stress results in adrenal CA release without increasing TH RNA. Intrauterine growth retardation from chronic prenatal hypoxemia results in neonatal CA depletion and decreased CA responsiveness. We speculate that chronic hypoxia alters CA pathways, increasing the susceptibility of these infants to later stressors.

Adaptation, Physiological↗

PubMed1993

Cholinergic regulation of rat preproenkephalin RNA in the adrenal medulla.

Expression of the rat preproenkephalin (ppENK) gene involves transsynaptic cholinergic mechanisms. We evaluated the effects of cholinergic agonist treatments in vivo on the expression of adrenomedullary ppENK RNA. Cholinergic treatment with nicotinic + muscarinic receptor agonists resulted in a synergistic 100-fold rise in steady-state ppENK messenger RNA levels, but only a 30- to 35-fold rise in initiation of steady-state ppENK RNA transcripts. The levels of initiated ppENK steady-state RNA peaked at two days, whereas mature (1.45 kb) ppENK mRNA levels continued to rise, peaking at four days. This suggested that other transcriptional (attenuation or alternative splicing) or post-transcriptional (RNA stabilization) regulatory mechanisms must be operative. As multiple ppENK RNA start sites exist, we examined how usage of multiple sites was altered by cholinergic treatments. The predominant start site changed from E2 in the basal state, to E4 after primary cholinergic stimulation, to E3 after re-treatment. This represents novel example of differential usage of multiple RNA initiation start sites in vivo. Differences in initiated and mature transcripts are consistent with at least four mechanisms involved in control of cholinergic-induced ppENK RNA expression: (i) simply new initiation of RNA transcripts, (ii) differential usage of the multiple RNA start sites, (iii) stabilization of mRNA transcripts, and (iv) attenuation and/or alternative RNA splicing of RNA transcripts.

Adrenal Medulla↗

PubMed1992

Tissue- and treatment-specific usage of multiple preproenkephalin transcriptional start sites.

The significance of the 5' heterogeneity of the transmitter gene ppEnk was evaluated by comparing start site usage (E1-E4) between 12 tissues from untreated rats, using primer extension analysis. In the basal state, we found that E3- and E4-initiated transcripts accounted for 80% of the total striatal RNA present compared with a preferential usage of the E2 start site in all other tissues. To determine whether this selective expression could be modified by biologically relevant pathways, rats were made hypoglycemic. After insulin shock, only E3 + E4-initiated transcripts increased (16-fold at 1 day) in the adrenal medulla but were unaffected in the striatum. As the effects of insulin shock on the adrenal medulla are mediated by cholinergic pathways and the striatum also receives cholinergic inputs, we also compared the effects of cholinergic drug treatments on start site usage in these two tissues. Rats were treated with cholinergic agonists (nicotine + oxotremorine) which induced adrenomedullary E2 and E3 + E4 transcripts (5- and 80-fold, respectively). This effect peaked at 2 days. In contrast, in the same animals, striatal ppEnk RNA (E3 + E4) increased only 10-15-fold after drug treatment. Hence it appears that biologically relevant whole animal stimuli (insulin shock or cholinergic agents) activate biochemical pathways, which affect start site usage in a tissue-specific fashion. Selective RNA start site usage suggests a biological significance, which may be important in the widespread tissue expression of this gene.

Adrenal Medulla↗

PubMed1992

Regulation of adrenomedullary preproenkephalin mRNA: effects of hypoglycemia during development.

To further evaluate whether transsynaptic mechanisms account for stress-induced changes in adrenomedullary preproenkephalin mRNA (ppEnk mRNA), neonatal rats were made hypoglycemic at a time when synapses are non-functional (less than 10 days postnatal age). While ppEnk mRNA in medullae from adult rats increased as much as 60-fold in this paradigm (insulin 10 U/kg), ppEnk mRNA levels in the newborn increased only 1.6-fold (insulin 20 U/kg). To evaluate whether postsynaptic cholinergic pathways of the neonatal adrenal medulla were functional, we treated 5-day-old pups with cholinergic agonists (nicotine [1 mg/kg, s.c., q 12 h] + carbachol [1.7 mumol/kg, s.c., q 12 h x 4 days]). Combined cholinergic agonist treatment augmented enkephalin prohormone and peptide levels up to 3-fold (P less than 0.05). To determine whether the blunted response to hypoglycemia in the newborn resulted from a deficiency in functional transsynaptic activity, synapses were matured using thyroid hormone pretreatment (postnatal days 2 and 3) before hypoglycemic stress. Hypoglycemia now caused a 40-fold increase in adrenomedullary ppEnk mRNA levels only in the T3/insulin treated group. To exclude other secondary effects of hypoglycemia (eg. hormonal, or insulin treatment-dependent), intracellular glycopenia was produced in the presence of secondary hyperglycemia by injecting adult rats or pups with 2-deoxyglucose (500 mg/kg). Similar to the insulin-hypoglycemia group, a large increase in adrenomedullary ppEnk mRNA resulted in the adult but not in the 5-day-old neonatal adrenal medullae. We conclude that enkephalin biosynthesis, like co-stored catecholamines, is induced by a transsynaptic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1990

Multiple preproenkephalin transcriptional start sites are induced by stress and cholinergic pathways.

A major control of gene expression occurs at the level of initiation of RNA transcription. In the nervous system this is reflected in part by 5' end RNA heterogeneity of neural transcripts. We now report the characterization of four preproenkephalin (ppEnk) RNA initiation sites in the rat brain striatum. In the adrenal medulla two ppEnk transcriptional start sites were detected. Moreover, cholinergic induction of ppEnk RNA initiation was observed in the adrenal medulla, but not in the striatum. The converse was true following handling stress. Our observations suggest that selective start site usage and stimulus evoked induction of specific RNA initiation is tissue-specific. We speculate that start site usage and induction may provide separate mechanisms through which neuronal gene expression is controlled in anatomically, as well as functionally distinct neurohumoral structures.

Adrenal Medulla↗

PubMed1990

Bimodal regulation of adrenal opiate peptides by cholinergic mechanisms.

Physiologic stressors increase trans-synaptic impulse activity and result in adrenal catecholamine release and biosynthesis. To determine the effects of stress on the co-localized opiate peptide system, rats were cold stressed at 4 degrees C. While cold stress slightly decreased enkephalin levels, a more severe stress (wetting and cold) increased enkephalin levels by 95%. Examining trans-synaptic-cholinergic mechanisms, treatment with either nicotinic or muscarinic agonists alone resulted in no change in adrenal enkephalin content. However, treatment with both nicotinic and muscarinic agonists together resulted in a three-fold rise in enkephalin levels. To further examine cellular mechanisms, medullae were explanted in the presence of agents that increase second messenger cyclic nucleotide levels. Treatments that increase the levels of cAMP, the cyclic nucleotide associated with nicotinic receptor activation, prevented the rise in medullary enkephalin relative to control explants. In contrast, treatments that increased cGMP levels, the cyclic nucleotide associated with muscarinic receptor activation, had no effect on enkephalin content compared to control explants. However, in the presence of both forskolin (10 microM) plus db-cGMP (5 mM), enkephalin content rose three-fold over control explants. These data suggest that, distinct from catecholamine pathways, enkephalin levels can be positively or negatively regulated by the severity of a stressful stimulus, by cholinergic receptor mechanisms and by an interaction of cyclic nucleotide second-messenger pathways.

Adrenal Medulla↗

PubMed1986

Calcium.

Disorders of calcium homeostasis are frequent and seldom diagnosed in the Emergency Department. In both the adult and pediatric population, the causes of increased or decreased calcium are many, and the index of suspicion needs to be raised for these disorders. Selective ordering is warranted for patients with altered mental status, seizures, neuromuscular irritability, or in patients with diseases known to have abnormalities of calcium as a complicating factor. These include renal failure, multiple myeloma, metastatic cancer, granulomatous disease, and endocrinopathies.

Adult↗