摘要:

SummaryThis study defines the relationship between heart rate and metabolic rate in newborn infants and evaluates the accuracy of prediction of metabolic rate from heart rate. Continuous measurements of oxygen uptake, CO2production, respiratory quotient, and cumulative heart rate were performed using computerized, open‐circuit indirect calorimetry and on‐line electrocardiogram monitoring over periods of 1 to 24 hr (mean 4.5 hr). Metabolic rate was calculated from the individual oxygen uptake and respiratory quotient. Thirty‐five studies were performed in 16 infants (birthweight 0.75 to 3.1 kg; gestational age, 26 to 42 wk; mean ± S.D. age at study, 26.5 ± 15.7 days; study weight, 1.78 ± 0.5 kg). Metabolic rate (cal/kg · min) and heart rate (beats/min) were compared minute by minute (8269 measurements) and showed a close third degree polynomial relationship for heart rates of 110 to 230/min (y = −0.0000291x3+ 0.01685x2− 2.93x + 197;r= 0.99;P< 0.001); however, at heart rates above 140 beats/min, a linear relationship was found (r= 0.997;P< 0.001). From cumulated heart rate measurements, factors defining metabolic rate per heart beat were also determined: for each beat 51.8 ± 6.8 &mgr;l of oxygen/kg are consumed and 0.258 ± 0.03 cal/kg (1.1 J/kg) are expended. Despite the wide variation in birthweight, gestational age, method of feeding, and clinical characteristics, there was a remarkable consistency in the heart rate‐metabolic rate relationships.A further 10 studies were performed in a similar group of infants to assess the predictive value of the previously defined relationships and showed a mean percentage deviation of 5.7 ± 4% from the measured value.We conclude that in the varied group of newborns studied, heart rate correlates closely with metabolic rate and that cumulative heart rate measurements enable the estimation of metabolic rate in newborn infants. This provides a method of monitoring energy expenditure and caloric requirements over long periods.SpeculationThe “heart rate‐metabolic rate” relationship defined in this paper, could offer a simple method of estimating energy expenditure and, hence, energy requirements for newborn infants.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryThe fetal sheep heart responds to &bgr;‐adrenergic stimuli; however,in vivostudies show the response of the fetal heart is less than that of the adult heart. We used [3H]dihydroalprenolol (DHA) to study directly &bgr;‐adrenergic receptors in heart particulates of fetal sheep at term and adult sheep. [3H]DHA binding to fetal heart particulates was rapid, reversible (t1/2= 2.9 ± 0.3 min), stereoselective, saturable (101.2 ± 7.4 fmoles/mg protein), and of high affinity (4.8 ± 0.4 nM). The rank order of agonists competing for [3H]DHA binding was isoproterenol (0.32 ± 0.10 &mgr;M) > epinephrine (1.19 ± 0.23 &mgr;M) ⋍ norepinephrine (2.67 ± 0.69 &mgr;M), which is compatible with &bgr;1‐adrenergic potencies. [3H]DHA also bound to the adult sheep heart in a manner expected for &bgr;1‐receptors. No difference in the binding affinity of [3H]DHA or agonists' competition was demonstrated between the fetal and adult sheep heart. Comparison of the concentration of &bgr;‐adrenergic receptors in fetal and adult hearts was confounded by the choice of the denominator for unit expression. The concentration was higher in the adult when expressed as a function of protein content or 5′‐nucleotidase activity (0.52 ± 0.07versus1.12 ± 0.06). However, there was no difference when tissue weight, Na+− K+‐ATPase, or NaF‐stimulated adenylate cyclase was used. Furthermore, isoproterenol‐stimulated adenylate cyclase and cardiac contractile response to a threshold dose of isoproterenol were identical in the fetal and adult sheep heart. We conclude that &bgr;‐receptors can be studied with [3H]DHA in the fetal sheep heart, this receptor is qualitatively similar to the &bgr;‐receptor in the adult sheep heart, and it is unlikely that there is a difference in the concentration of &bgr;‐adrenergic receptors in fetal and adult sheep heart.SpeculationThe interactions of adrenergic agents with cardiac &bgr;‐adrenergic receptors in the term fetus are identical to those in the adult, and the receptor‐adenylate cyclase coupling system reaches maturity before birth.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryAsp1‐125I‐Tyr4‐angiotensin II (125I‐AII) was degraded during incubation with rat plasma or homogenates of liver or kidney. The electrophoretic profile of peptide fragments revealed that the disappearance of125I‐AII was first order and was accompanied by an accumulation of125I‐tyrosine in the incubation medium. The only other metabolites of angiotensin AII detectable by peptide mapping were the amino‐terminus tetrapeptide and the carboxy‐terminus hexapeptide. The appearance of these fragments was highly variable, suggesting that endopeptidases did not constitute the ultimate cleavage of angiotensin II hydrolysis. The half‐life of125‐AII in plasma or liver homogenates did not change with age (approximately 8 to 12 and 6 to 9 min, respectively). In contrast, the rate of disappearance of125I‐AII in homogenates of rat kidney depended upon the age of the rat from which the tissue was obtained. The half‐life of125AII decreased three‐fold (from approximately 8.3 to 2.8 min) between 2 wk after birth and adult (approximately 8 wk). This increase in the rate of metabolism of125I‐AII was accompanied by a concomitant two‐fold, age‐related increase in the rate of appearance of125I‐tyrosine in the reaction mixture containing renal tissue.SpeculationAge‐related differences in the activities of angiotensinase enzymes may be of considerable importance in regulating the concentration of angiotensin II in plasma and tissues of developing animals. When viewed in context of changes in renin and converting enzyme activities in rats, the increase in the rate of metabolism of angiotensin II is the only available evidence consistent with the decrease in plasma angiotensin II concentration between 6 and 8 wk of age.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummarySeventy children homozygous for Hb S (SS) and their 111 heterozygous (AS) parents were evaluated through their erythrocytic indices, hemoglobin composition, and occasionally throughin vitroHb chain synthesis values.Three groups of SS patients and of AS parents were identified based on differences in degree of microcytosis (MCV) and (degree of hypochromia (MCH) values. The level of Hb S in the Hb S heterozygotes showed a trimodal distribution. Five SS patients had an &agr;‐thalassemia homozygosity (&agr;0&agr;/&agr;0&agr;; &bgr;S/&bgr;S) which was characterized by a distinct microcytosis and hypochromia (MCV, ≤ 70 fl; MCH, ≤22 pg). Nine SS patients had an &agr;‐thalassemia heterozygosity (&agr;0/&agr;/&agr;&agr;; &bgr;S/&bgr;S) with an MCV value of 71 to 78 fl, and an MCH value of 21.3 to 26.5 pg. Four AS parents had an &agr;‐thalassemia‐2 homozygosity with values of MCV ≤ 71 fl and MCH ≤ 23.5. The level of Hb S was < 31%. Thirty‐nine AS parents had an &agr;‐thalassemia‐2 heterozygosity characterized by an MCV value of 72 to 79 fl, an MCH value of 23.6 to 26.5, and a level of Hb S ranging between 31.0 and 36.8%.The Hb A2level in SS patients was significantly correlated with the RBC counts and the MCV and MCH (r= 0.38, −0.52, and −0.47, respectively). Significant correlations in AS parents were also noted between the MCV, MCH, RBC, and Hb S percentages (r= 0.62, 0.68, and −0.49, respectively).Although the data are limited, the simultaneous occurrence of an &agr;‐thal‐2 homozygosity seems to decrease the level of Hb F in sickle cell anemia. The presence of an &agr;‐thal‐2 heterozygosity or homozygosity together with an SS or AS condition resulted in identifiable hematologic phenotypes.SpeculationThe occurrence of microcytosis and hypochromia among SS patients in association with increased erythrocyte counts and Hb A2percentages indicates the concomitant presence of &agr;‐thalassemia‐provided &bgr; chain deficiencies have been excluded through biosynthetic experiments or through family studies. The &agr;‐thal‐2 heterozygosity (&agr;0&agr;/&agr;&agr;; &bgr;S/&bgr;S), which is associated with a mild &agr; chain deficiency, results in a slight decrease of the degree of microcytosis and hypochromia values. On the other hand, the &agr;‐thal‐2 homozygosity (&agr;0&agr;/&agr;0&agr;; &bgr;S/&bgr;S) and perhaps also the &agr;‐thal‐1 heterozygosity (&agr;0&agr;0/&agr;&agr;; &bgr;S/&bgr;S), which are associated with a moderate &agr; chain deficiency, result in a distinct microcytosis and hypochromia. The high incidence of &agr;‐thal‐2 among Black Americans requires careful consideration and may be more prevalent than an iron deficiency anemia in children with the SS and AS conditions.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryContinuous intravenous infusion of the short‐chain fatty acid octanoate into rabbits results in significant increases in intracranial pressure by 2 hr of infusion. Pressure waves are also observed. Muscular paralysis has a protective effect on in tracranial pressure. This study has potential implications for the better understanding and more effective treatment of Reye's syndrome.SpeculationIntravenous infusion of sodium octanoate in rabbits produces an experimental model of Reye's syndrome, including elevated intracranial pressure. This model will be useful to test new therapeutic modalities for control of intracranial pressure in this disorder.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryWe describe the interrelationship of the urinary excretion of sodium, calcium, magnesium, and phosphorus in 22 hypocalcemic premature neonates whose mean gestational age was 31.7 wk. Strong relationships between sodium excretion and calcium excretion (r= 0.85), sodium excretion and magnesium excretion (r= 0.76), sodium excretion and phosphorus excretion (r= 0.61), and calcium excretion and magnesium excretion (r= 0.94) were demonstrated. Sodium intake during the 84‐hr study period ranged from 2.9 to 34.5 mEq/kg and calcium intake during the same period ranged from 0 to 152.3 mg of elemental calcium per kg. The intakes of the other cations were negligible. All variables but phosphorus excretion (r= −0.55) were independent of calcium intake whereas sodium excretion (r= 0.76), calcium excretion (r= 0.72) magnesium excretion (r= 0.62), and phosphorus excretion (r= 0.53) were all correlated with sodium intake. Serum calcium concentration at the end of the study was unrelated to total calcium intake during the 84‐hr study period, whereas it was negatively related to total sodium intake (r= −0.71).SpeculationWe suggest that sodium intake and sodium exeretion exert significant control over the excretion of calcium, magnesium, and phosphorus in sick, hypocalcemic, premature neonates. High sodium intake in this group of patients is associated with a lowered serum calcium concentration; thus, increased sodium intake and perhaps increased calcium excretion may play a role in the development or exacerbation of early onset neonatal hypocalcemia.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryThe basal adenylate cyclase activities, per g wet wt, of homogenates of adult skeletal muscle (4 ± 0.4 S.E. nmoles/10 min · g wet wt−1) were lower than those values in 150‐ and 80‐day fetal muscle (18 ± 1.2 and 23 ± 1.6 S.E. nmoles/10 min · g wet wt−1). This difference in enzyme activity relative to growth was also apparent in the 100,000 ×gparticulate fractions of adult muscle (2.5 ± 0.2 S.E. nmol/10 min·g wet wt−1) compared to the 150‐and 80‐day fetal muscle (12 ± 1.5 and 14 ± 1.9 S.E. nmoles/10 min·g wet wt−1). The fluoride‐stimulated adenylate cyclase activities of the homogenates and particulates and the increases in enzyme activity with fluoride were also at least four‐fold greater in 80‐ and 150‐day fetal than in adult muscle. When basal adenylate cyclase activities of homogenates were compared on the basis of the nitrogen content of the fraction analyzed rather than on the wet weight of the original samples, the differences in enzyme activities of the adult compared to the fetal series were even greater because of the lower nitrogen content of fetal muscle (1.8 ± 0.2 S.E. nmoles/10 min·10 mg N−1for the adult series and 10.2 ± 0.7 and 22.2 ± 1.2 S.E. nmoles/10 min·10 mg N−1for the 150‐and 80‐day series). The difference in activity with age was again apparent in the 100,000 ×gparticulate fractions (1.9 ± 0.2 S.E. nmoles/10 min·g wet wt−1for the adult series and 9.8 ± 0.9 S.E. and 24 ± 2.2 nmoles/10 min·g wet wt−1for the 150‐ and 80‐day series). Because the nitrogen content of the 80‐day fetal muscle was less than that of the 150‐day series, the adenylate cyclase activities per mg N were highest in the younger fetal series. In the presence of guanylylimidodiphosphate the percent increase in adenylate cyclase activity was two to three times greater in the fetal particulate preparations than in the adult and was concentration‐dependent in both series.The basal guanylate cyclase activities for both the 100,000 ×gsupernatant and particulate fractions were higher in 80‐day fetal than in adult muscle; two‐ to three‐fold higher in terms of wet wt and over six‐fold higher in terms of nitrogen. Both the absolute and percentage increases in activity of the fetal particulate enzyme with Triton were at least twice those of the adult. Triton had no effect on the enzyme activity of the 100,000 ×gsupernatant fraction of either series. The concentration of cyclic adenosine 3′: 5′‐monophosphate was 8 to 10 times higher in rapidly growing than in adult muscle, and the concentration of cyclic guanosine 5′‐monophosphate was 26 to 62 times greater.SpeculationThere is a striking difference in the degree of maturation at birth of skeletal muscle in different species of animals. Skeletalmuscle from the rhesus fetus is particularly suitable for study if one is interested in human fetal muscle metabolism because the maturation rate of this tissue (on the basis of percent of gestation) is similar in the two species. Because fetal tissues must proliferate and differentiate, they must perform synthetic processes at a rapid rate, and synthetic processes are expensive in terms of energy. Therefore, it is not surprising that a number of fetal enzymes are more active than are those of the adult. In addition, a greater sensitivity of fetal enzymes to effector molecules may further magnify the activity of these enzymes. It would be of interest to measure the cyclic nucleotide‐dependent protein kinase activities in fetal and adult rhesus muscle. Recent evidence suggests possible differences in the functions of types I and II cAMP‐dependent protein kinases in relation to cellular growth and differentiation. Studies of these kinases in rhesus fetal muscle during the predominantly proliferative phase (earlier than 85 days gestation) and during the period when differentiation is predominant (85 to 110 days) should be of value in studying the biologic significance of these kinases.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryContinuous measurements of minute ventilation (&OV0312;I), oxygen consumption (&OV0312;O2), heart rate (HR), activity, and temperature were made in eleven low birth weight infants during the interval between feedings. Significant increases in &OV0312;I, &OV0312;O2, and HR were noted between quiet and active sleep. (&OV0312;I Active− &OV0312;I Quiet/&OV0312;I Quiet) × 100 = 18.4% &OV0312;O2 Active− &OV0312;O2 Quiet/&OV0312;O2 Quiet) × 100 = 10.1% and HRActive− HRQuiet/HRQuiet) × 100 = 6.4%. Significant differences were also noted within epochs of the same state of sleep: mean slope &OV0312;Iversustime in epoch (t) = −156 ml/kg·min/hr, &OV0312;O2versust. = 1.49 ml/kg·min/hr and HRversust = −15.0 beats/min/hr. Differences between successive epochs of the same state of sleep were also observed: &OV0312;I, +5.9 to 46.6%; &OV0312;O2, 4.7 to 24.6%; HR, 1.0 to 9.7%. These differences were related to the length of time after feeding. These data indicate that steady state conditions do not occur in growing low birth weight infants and that the design of studies of respiration and metabolism in these infants should include continuous assessment of the state of sleep or activity and time after feeding to ensure that experimental and control periods are truly comparable.SpeculationThe significant variability in minute ventilation, oxygen consumption, and heart rate which occurs spontaneously in low birth weight infants secondary to changes in activity and postprandial interval must be acknowledged in the design of clinical research. It is probable that these factors influence not only mean levels of metabolic and respiratory activity but also the sensitivity to experimental stimuli such as hypoxia, hypercarbia, and drugs.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryWhen logarithmically growing neuroblastoma cells were exposedin vitrofor 24 hr to a range of concentrations of various antitumour drugs and then cloned in agar to assess colony‐forming ability, the dose‐response curves obtained were of two types only, namely exponential—plateau or exponential. The former category, included hydroxyurea, 1,1′‐propylene bispiperazine‐3,5‐dione (ICRF‐159), vincristine and vindesine, where the plateau was reached before 1 log cell kill, and 4′‐demethylepipodophllotoxin thenylidine glucoside (NSC 122819) (VM‐26) and 4′‐demethyl‐epipodophllotoxin‐9‐(4,6‐oethylidine‐&bgr;‐D‐glucopyranoside (NSC 141540) (VP‐16‐213), where the plateau occurred at approximately 5% survival. Exponential survival curves were obtained with actinomycin D, Adriamycin, bleomycin,cis‐dichlorodiammine platinum (II) (cis‐platinum), dibromodulcitol, 5‐fluorouracil, 4′‐(9‐acridiny‐lamino)methanesulfon‐m‐anisidine (NSC 249992) (mAMSA), melphalan, and peptichemio. A comparison of drug concentrations required to reduce survivalin vitroby 70%, with a 24‐hr drug exposure, was attempted with those concentrations achievable as plasma levels in man after conventional drug therapy. The results obtained, after many and varied assumptions, allowed the division of the drugs tested into three main groups: (1) most effective agents, including mAMSA, VM‐26, and Adriamycin; (2) agents with some activity—vincristine, vindesine, VP‐16‐213,cis‐platinum, melphalan, and peptichemio, although only when the latter three drugs were used at the higher dosage levels; (3) agents with little, if any, activity—actinomycin D, bleomycin, dibromodulcitol, 5‐fluorouracil, hydroxyurea, and ICRF‐159. In terms of attempting clinical correlations, available data suggest definite value in treating neuroblastoma with VM‐26 and Adriamycin [from our group (1)] and also with vincristine, melphalan (high dose), peptichemio, andcis‐platinum [from our group (2)]. No significant clinical activity has been reported for actinomycin D nor for bleomycin in previously treated children, and both these drugs proved negative in this model test system. Among the newer agents tested experimentally, our results suggest that although clinical evaluation of mAMSA, VP‐16‐213, and vindesine might be profitable, dibromodulcitol and ICRF‐159 may prove inactive.SpeculationThe dismal prognosis for the majority of children with neuroblastoma serves to highlight the need for new and more effective therapies. One approach is to attempt to screen experimentallyin vitrofor drugs effective in this disease. Our preliminary studies, using only one cell line derived from one portion of a human tumour, have suggested, with many reservations, some correlations betweenin vitroand clinical data. This work is now being extended to consider other human neuroblastoma cell lines and to monitor retrospectively drug responsesin vitrowith clinical responses. These studies are essential before any attempts are made to extrapolate any of thein vitroresults to humans.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SummaryTo explore further the factors that underly the deficient generation of 3,5,3′‐triiodothyronine (T3) from thyroxine (T4) (T3‐neogenesis) in fetal liver, studies were performed in homogenates and subcellular fractions of liver from pregnant rabbits and their corresponding fetuses. In whole homogenates, T3‐neogenesis (percentage added T4:50 mg protein) during 3 hr incubations of specimens from fetuses proceeded at a much slower rate (1.7 ± 0.5, mean ± S.D.) than in specimens from the corresponding does (1.4 ± 5.3). Dithiothreitol (DTT, 20 mM), a known stimulant of T3‐neogenesis, did not significantly alter the activity of fetal specimens (2.6 ± 1.3), but significantly increased activity in those obtained from does (18.2 ± 7.4). To investigate the basis for these differences, additional experiments were performed in which microsomal and cytosolic fractions from fetal and maternal livers were variously mixed and T3‐neogenesis was assessed in the presence and absence of DTT. Activity of fetal microsomes was consistently less than in maternal microsomes, regardless of the source of the cytosols with which they were incubated. Further, mixtures containing fetal microsomes were not stimulated by DTT, whereas those containing maternal microsomes were. In addition to this evidence of an abnormality with respect to the fetal enzyme, evidence was obtained of a concomitant abnormality in fetal cytosol fractions. Thus, T3‐neogenesis by maternal microsomes was consistently greater when incubated with maternal cytosol than with fetal cytosol, presumably owing to lesser support of T3‐neogenesis by cofactors known to be present in cytosol. Additional evidence of an abnormality in the microsomal enzyme of the fetus was obtained in studies of the kinetics of T3‐neogenesis. In the presence of DTT, derived values for the Kmof the fetal enzyme were approximately 10‐fold higher than were those for the maternal enzyme (5.9 ×−5and 7.1 × 10−6M).The studies suggest that the defective generation of T3from T4seen in fetal liver from other species is also present in the liver of the fetal rabbit. Lower activity in the fetal liver is due in part to a lesser activity of cytosolic cofactors, but mainly to an abnormality in the T3‐generating enzyme, reflecting either a lower concentration of enzyme, a lesser responsiveness to stimulatory cofactors, or a combination of the two.SpeculationThe enzyme in fetal liver that converts thyroxine to 3,5,3′‐triiodothyronine behaves differently from that in maternal liver with respect to its affinity for substrate and its response to stimulatory sulfhydryl cofactor. Fetal enzyme may be an isozymic variant of the adult enzyme, as has been reported for other hepatic enzymes. The relation between fetal and maternal enzymes may be analogous to that which exists with respect to enzymes of normal and malignant tissue.

ISSN:0031-3998    

出版商:OVID    

年代:1981

数据来源: OVID