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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical application of caffeine for the treatment of neonatal apnoea was considered in 57 low birth weight infants (less than 1500 g birth weight). The rationale for the study was that transdermal absorption of drugs and chemical agents has been demonstrated in neonates depending on anatomical and functional immaturity of the epidermal barrier. Considering these issues we studied the efficacy of percutaneous application of caffeine using high pressure liquid chromatography (HPLC) for evaluation of its plasma levels. 2 x 7.5 mg (babies less than 1000 g, extremely low birth weight [ELBW] or 2 x 10 mg (babies greater than 1000 g, very low birth weight [VLBW]) of caffeine were applied transcutaneously in form of a gel to the abdominal skin (Standard dose = 0.06 g of gel equivalent to 10 mg of caffeine citrate). Gestational age of our patients was 29.4 +/- 1.7 weeks, mean birth weight 1025 +/- 240 g. Mean postnatal age at beginning of treatment was 25.5 +/- 18 h. Of the treated babies, 73% had serum levels in therapeutic range about 48 h after the first dose of caffeine application. After 10 doses 97% of patients had serum levels in the therapeutic range. We conclude that percutaneous caffeine application is a safe and useful approach for treatment of apnoea in VLBW and ELBW infants.
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PMID:Percutaneous caffeine application in the treatment of neonatal apnoea. 195 66

In apneic premature infants treated with theophylline or caffeine the pharmacokinetics of the methylxanthines were investigated. Orally applied caffeine and theophylline were rapidly absorbed reaching peak plasma levels at 1-2 and 1-4 h resp. The plasma concentration of free theophylline was significantly higher (p less than 0.001) in prematures than in adults. In prematures and adults only 5 resp. 8% of caffeine were bound to the plasma proteins. The salivary methylxanthine concentration corresponds to the plasma concentration of the free drugs. The mean plasma half-live of theophylline was 22.3 h, the clearance 28.3 ml/kg/h and the volume of distribution 0.9 l/kg. For caffeine a plasma half-live of 70.6 h, a clearance of 8.6 ml/h/kg and a volume of distribution of 0.84 l/kg was found. A first oral dose of 7-9 mg/kg theophylline or caffeine should be administered to reach rapidly effective plasma concentrations of about 10 micrograms/ml. To maintain a mean plasma concentration of about 10 micrograms/ml, a daily oral maintenance dose of 5-9 mg/kg theophylline or 2 mg/kg caffeine should be given. High concentrations of unchanged caffeine and theophylline were excreted in the urine of premature infants indicating immaturity of the metabolizing hepatic enzymes. In prematures treated with theophylline caffeine was found in plasma as a metabolite of theophylline.
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PMID:[Pharmacokinetics of theophylline and caffeine in premature infants with apnea (author's transl)]. 732 25

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.
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PMID:Effect of pregnandiol on caffeine metabolism in female rats. 824 2

Spermatozoa mature during epididymal transit, acquiring the abilities to swim progressively, fertilize oocytes, and produce viable offspring. In this study, we investigate the capacity of spermatozoa retrieved from the midcorpus and distal cauda regions of the epididymis of the cynomolgus monkey to penetrate homologous zona pellucida. Successful in vitro fertilization by ejaculated macaque sperm is dependent upon the addition of caffeine and dbcAMP. Therefore, the effect of these cyclic nucleotide mediators was also examined in this study. Results of sperm motion analysis indicate no difference in baseline values (without stimulators) for any motion parameter. With the addition of caffeine and dbcAMP, curvilinear velocity significantly increased only for the distal cauda sperm (P = 0.05). Amplitude of the lateral head displacement was significantly increased for distal cauda sperm (P < 0.01); although elevated above baseline, the increase observed after activation by corpus sperm was significantly lower than that achieved by cauda sperm (P < 0.05). The addition of caffeine and dbcAMP was an absolute requirement for zona penetration by both midcorpus and distal cauda sperm. With activation, zona penetration was significantly decreased for corpus sperm compared to cauda sperm (P < 0.001). These results suggest that cynomolgus monkey sperm reaching the midcorpus region of the epididymis have not completed all of the maturational changes requisite for successful fertilization; this immaturity is evidenced by decreased sperm motion and by impedance at the level of zona penetration.
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PMID:Effects of caffeine and dbcAMP on zona pellucida penetration by epididymal spermatozoa of cynomolgus monkeys (Macaca fascicularis). 905 45

Mature myocardium utilizes calcium released by the sarcoplasmic reticulum (SR) for cell contraction. Transient exposure of mature myocytes to caffeine is known to directly trigger Ca2+ release from the SR. In contrast, neonatal rabbit heart cells rely on transsarcolemmal Ca2+ influx for tension generation. SR function is decreased in immature heart and appears to play a minimal role as a calcium source. Accordingly, we hypothesized that neonatal rabbit myocytes would not respond to a caffeine pulse. Isolated neonatal and adult myocytes were paced to load the SR with calcium and then exposed to a 1-s pulse of 10 mM caffeine. As previously described, adult myocytes exhibited a brisk contraction in response to caffeine. Unexpectedly, neonatal myocytes also exhibited a similar, brisk response. These caffeine-induced contractions were not dependent on extracellular Ca2+ but were dependent upon the loading of SR Ca2+ stores. When SR Ca2+ stores were depleted by exposure to caffeine, mature myocytes exhibited only small, slow contractions in response to electrical field stimulation. Replenishing the SR Ca2+ stores resulted in normal, brisk contractions. In contrast, electrically stimulated contractions in immature myocytes were largely unaffected by caffeine-induced SR depletion. Thus, although neonatal myocytes are capable of loading and releasing calcium from the SR, such SR calcium release is not normally required for contraction in the developing heart. The minor role of SR Ca2+ release in immature rabbit heart may not result from immaturity of the SR, but rather from an inadequate mechanism to trigger SR calcium release.
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PMID:Caffeine-induced contractions in developing rabbit heart. 928 67

The purpose of the present study was to determine whether age-related changes in the expression and function of the cardiac isoform of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) play a role in SR Ca(2+)release and cell contraction. SERCA2a protein levels and subcellular localization were compared between fetal, neonatal, juvenile and adult New Zealand White rabbits. Studies of SERCA function in isolated myocytes were performed in situ by examining the rate of reloading of the SR Ca(2+)stores following caffeine-induced depletion. We found that significant quantities of SERCA2a were present early in immature heart and that SERCA2a expression reached adult levels within 15-30 days after birth. Furthermore, SERCA2a protein is present as a series of transverse striations within the cell as early as 1 day of age. In contrast to previous studies of SERCA in vitro, the SERCA protein function in situ was found to be comparable between neonatal and adult myocytes in maintaining SR Ca(2+)stores. These results indicate that the paucity of SR Ca(2+)release in immature ventricular cardiac myocytes is not the result of immaturity in SERCA2a expression.
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PMID:Sarcoplasmic reticulum Ca(2+)ATPase and cell contraction in developing rabbit heart. 1077 80

Apnea of prematurity (AOP) is a common problem that affects premature infants and, to a lesser degree, term infants. Apnea of prematurity appears to be due to immaturity of the infant's neurologic and respiratory systems. Apnea of prematurity is a diagnosis of exclusion that can be made only when other possible infectious, cardiologic, physiologic, and metabolic causes of apnea have been ruled out. The fundamental principles for managing apnea of prematurity include monitoring the infant closely while instituting supportive care measures such as tactile stimulation, continuous positive airway pressure, or mechanical ventilation. When necessary, pharmacologic therapy may be used to stimulate breathing. The first-line agents of choice for the management of AOP are the methylxanthines. And, for second-line therapy, a switch to a different class of agent, such as the respiratory stimulant doxapram, is an option. Of the methylxanthines, theophylline is the most extensively used. However, a review of the literature suggests that caffeine citrate may be the agent of choice for AOP. Comparative clinical studies have demonstrated that caffeine is at least as effective as theophylline, has a longer half-life, is associated with fewer adverse events, and, in addition, has a greater ease of administration. Caffeine stimulates the respiratory and central nervous systems more effectively and penetrates into the cerebrospinal fluid more readily than theophylline. In addition, because of stable plasma levels, caffeine has a wide therapeutic margin and few side effects. In contrast, theophylline plasma levels may fluctuate widely, which necessitates frequent monitoring and has a higher incidence of adverse events than caffeine. Before the FDA approval of caffeine citrate (Cafcit) for administration either intravenously and/or orally, caffeine preparations were "homemade." A few studies suggest that use of pharmacotherapy to treat AOP is not generally associated with long-term sequelae, although more data are needed before this can be definitively concluded.
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PMID:Current options in the management of apnea of prematurity. 1087 34

Dihydropyridine receptors (DHPRs), ryanodine receptors (RyRs), and triadin are major components of triads of mature skeletal muscle and play crucial roles in Ca2+ release in excitation-contraction (E-C) coupling. We investigated the expression and localization of these proteins as well as intracellular Ca2+ transients during development of human muscle cells cultured aneurally and innervated with rat spinal cord. mRNAs encoding skeletal muscle isoforms of the DHPR alpha1 subunit (alpha1S-DHPR), the RyR, and triadin were scarce in myoblasts and increased remarkably after myotube formation. Immunocytochemically, alpha1S-DHPR was expressed after myoblast fusion and localized mainly within the cytoplasmic area of aneural myotubes whereas the cardiac isoform (alpha1C-DHPR) was abundant along the plasma membrane. RyRs and triadin were both detected after myotube formation and colocalized in the cytoplasm of aneural myotubes and innervated muscle fibers. Along the plasma membrane of aneural myotubes, colocalization of alpha1C-DHPR with the RyR was more frequently observed than that of alpha1S-DHPR. In innervated muscle fibers, alpha1S-DHPR and RyR were colocalized first along the plasma membrane and later in the cytoplasmic area and formed regular double rows of cross-striation. The alpha1C-DHPR diminished after innervation. In Ca2+ imaging, spontaneous irregular slow Ca2+ oscillations were observed in aneurally cultured myotubes whereas nerve-driven regular fast oscillations were observed in innervated muscle fibers. Both caffeine and depolarization induced Ca2+ transients in aneurally cultured myotubes and innervated muscle fibers. In aneurally cultured myotubes, depolarization-induced Ca2+ transients were highly dependent on extracellular Ca2+, suggesting immaturity of the Ca2+ release system. This dependence remarkably decreased after innervation. Our present results show that these proteins are expressed differently in aneurally cultured myotubes than in adult skeletal muscle, that Ca2+ release in aneurally cultured myotubes is different from in adult skeletal muscle, and that innervation induces formation of a mature skeletal muscle-like excitation-contraction coupling system in cultured human muscle cells.
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PMID:Triad proteins and intracellular Ca2+ transients during development of human skeletal muscle cells in aneural and innervated cultures. 1120 30

Apnea in a premature infant is not always due to immaturity and caffeine is not always the answer. We report a case of apnea in a preterm infant who presented at two weeks of life with increase in frequency of apnea that did not respond to caffeine. Family history was significant for diarrhea in a sibling. Stool PCR was positive for Norovirus Genogroup II. Enteric isolation was instituted and the apnea resolved spontaneously with conservative management. Re-emergence of apnea or persistent apnea necessitates further investigation to elucidate the etiology.
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PMID:Non-Rotavirus infection causing apnea in a neonate. 1990 39

Prematurity apnea remains a major clinical problem that requires treatment choices which are sometimes difficult. Prematurity apnea occurs in most infants of gestational age at birth less than 33 weeks. It is a developmental disorder which usually reflects a "physiological" immaturity of respiratory control. However, neonatal diseases may be associated and play an additive role, resulting in an increased incidence of apnea. Careful screening should therefore be performed in order to make sure that no other factor than immaturity is involved in the occurrence of apnea. Short apnea (less than 10s, without hypoxemia and bradycardia), due to immaturity, are not clinically relevant. More prolonged apnea, that last for more than 15 or 20s, and / or apnea associated with bradycardia or oxygen desaturation, results in short-term disturbances of cerebral haemodynamics and oxygenation, which may negatively impact on neurodevelopmental outcome. Evaluating the immediate severity of apnea and the risks that apnea may affect long-term outcome remains a challenge. The choice of treatments is based on a few evidences. Caffeine citrate, which reduces the incidence of apnea, has been used for decades. However, a thorough evaluation of risks and benefits of this medication has been performed only recently. Caffeine citrate was found to be safe and resulted in unexpected benefits. In treated infants, compared with controls, indeed, a decreased incidence of the following complications was recorded: bronchopulmonary dysplasia at 36 weeks of conceptional age, patent ductus arteriosus, cerebral palsy at 18 months of age. Nasal CPAP can be used in association with caffeine citrate, when the latter is not effective enough.
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PMID:[Apnea of prematurity: what's new?]. 1994 73


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