摘要:

The differences in the immediate (30 sec or l min) and late (5 min) ventilatory response to high and low O2have not been quantitated in preterm infants and adult subjects using the same methods. It was thought that these differences might explain the paradoxical ventilatory response to CO2at various O2concentrations in preterm infants (12). Thus, 9 preterm infants and 10 adult subjects were given 21% O2to breathe and then 100 or 15% O2for 5 min each. Adults also breathed 15% O2before 100% O2or 12% O2in order to make their resting arterial PO2more comparable to those of infants breathing 21% O2. The ventilatory response to 100% O2was the same in preterm infants and adult subjects, but the late response to 15% O2remained paradoxical, ventilation decreasing at 5 min by 18% in infants and increasing by 19% in adults. The authors conclude: 1) the traditional concept of the ventilatory response to 100% O2being different in infants and adult subjects is false; 2) the notion that the response to low O2is paradoxical in infants is correct; and 3) the data do not explain why the response to CO2under various background concentrations of O2in infants is the reverse of that in adult subjects, but the depressed ventilatory response to hypoxia in infants may justify, at least in part, their flatter response to CO2during low O2breathing.Speculation The findings suggest that the response of preterm infants to high and low O2per se is not the cause of the paradoxical response to CO2under various background concentrations of O2. If it were, it would be expected that the response to low and high O2would differ in infants and adults. This was true for hypoxia only, the response to hyperoxia being the same in infants and adults. The speculation, therefore, is that differences in cerebral blood flow caused by CO2and O2interaction may be responsible for the paradoxical response to CO2.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

A random sample of 46 families with single and multiple cases of spina bifida has been selected from families referred to the Institute of Pediatrics for genetic counseling. This sample constituted a group of 92 parents and 102 offspring: 41 normal, 46 with spina bifida, and 13 with spina bifida occulta. Routine HLA typing was performed on the parents and their children. For each case, 13 HLA specifities from locus A and 15 from locus B were determined. Segregation analysis in families showed excellent agreement with the expected values. HLA gene frequencies in the affected children as compared with a control population of 240 normal adults, revealed significantly higher frequency for HLA-B27 allele: x2= 11.9515,P(corrected for the number of alleles) < 0.028. A significant relative risk of spina bifida development for a given HLA-B27 antigen was 2.7. In view of the presented results, routine HLA typing might be recommended for genetic counseling as a new tool for identification of high risk families.Speculation A number of developmental genes mapped at the T locus in mice may interact in heterozygotes to produce offspring which are tailless or have spina bifida. Close chromosomal proximity of the T locus and the H-2 complex, as well as their evolutionary relationship, suggest that H-2 antigens might be considered as genetic markers of developmental events. The great homology between the H-2 chromosomal region in mice and the human HLA complex suggested the investigations on association between his-tocompatibility antigens and birth defects in man.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

In 16 anesthetized piglets, the effects of 1-deamino-8-D-argininc-vasoprcssin (DDAVP) upon urinary flow rate, relative urinary osmolarity (U/Posmol), fractional water excretion (U/PIn), fractional urta excretion (U/Purea/U/PIn), renal adenosine 3',5'-cyclic monophosphate (c-AMP) formation rate, and medullary c-AMP content were studied during the first 6 days of life. Glomerular filtration rate (GFR) was 0.19 ± 0.09 ml/min/g kidney wt (means ± SD) on day 1 and increased to 0.51 ± 0.11 ml/min/g kidney wt on day 6. It was not affected by the application of 20 μg DDAVP/ kg body wt. On day 1, U/Posmol(1.81 ± 0.29), urinary flow rate (5.36 ± 1.49 μl/min/g kidney wt), U/PIn(31.67 ± 6.10) and U/ Purea/U/PIn(0.84 ± 0.12) were not affected by DDAVP application. From day 2 onward, the reponse of these variables to application of DDAVP increased progressively. On day 6, the following responses were observed: Urinary flow rate decreased from 13.85 ± 7.02 μl/min/g kidney wt before DDAVP to 5.07 ± 2.19 μl/min/ g kidney wt after DDAVP. U/Posmolraised from 1.24 ± 0.27 before DDAVP to 2.64 ± 0.17 after DDAVP. U/PInincreased from 36.85 ± 13.11 before DDAVP to 109.39 ± 22.00 after DDAVP. U/Purea/U/PIndecreased from 0.75 ± 0.05 before DDAVP to 0.55 ± 0.04 after DDAVP. These data indicate that the small solute permeability of the medullary collecting ducts becomes increasingly sensitive to antidiuretic hormone (ADII) during this period.The increase in responsiveness of the urinary concentrating system with age was paralleled by the effect of DDAVP on renal c-AMP formation rate. In the diuretic control state, no correlation between renal c-AMP formation rate and the number of days was observed. However, after the application of DDAVP, the nephrogenic fraction of renal c-AMP excretion rate increased from 10.58 ± 4.49 pmole/min/g kidney wt on day 1 to 21.61 ± 8.10 pmole/ min/g kidney wt on day 6. Similar results were observed with the medullary c-AMP content. In diuretic control animals which had not received DDAVP, the medullary c-AMP content ranged between 636 ± 257 pmole/g wet wt on day 1 and 622 ± 75 pmole/g wet wt on day 6. However, in animals which had been infused with DDAVP, medullary c-AMP content increased from 684 ± 274 pmole/g wet wt on day 1 to 1536 ± 316 pmole/g wet wt on day 6.Speculation The unresponsiveness of the medullary adenylatecyclase to ADII in the newborn kidney might restrict, in addition to other parameters, the renal concentrating ability during the neonatal period.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The effects of 18 normally occurring and 11 patalogical metabolites of the branchcd-chain amino acids on the glycine cleavage system were investigated on intact rat liver mitochondria. It was demonstrated, that 2-oxo-isovaleric acid, 2-methyl-butyric acid, and isobutyric acid significantly inhibited the glycine cleavage system in intact mitochondria.Further studies on the solubilized glycine cleavage system demonstrated that the inhibitory effect was due to 2-methyl-butyryl-CoA (linear noncompetitive inhibition, ki: 0.1–0.15 mM) and isobutyryl-CoA (S-hyperbolic, I-linear noncompetitive inhibition, ki: 0.2–0.3 mM). Both 2-methyl-butyric acid and isobutyric acid exhibited less inhibition (2-methyl-butyric acid: competitive inhibition, ki: 5.5 mM, isobutyric acid: competitive inhibition, ki: 16 mM), while 2-oxo-isovaleric acid was without inhibitory effect, and probably affects intact mitochondria through transformation to isobutyryl-CoA.It is suggested that the inhibitory action of 2-methyl-butyryl-CoA and isobutyryl-CoA may explain the hyperglycinemia seen in propionyl-CoA carboxylase deficiency, methyl-malonyl-CoA mutase deficiency and ß-ketothiolase deficiency.Speculation In patients not suffering from any known inborn error of metabolism, hyperglycinemia has been described in connection with two circumstances, namely, severe generalized illness and medication with dipropylacetic acid. Because both these conditions might cause some derangement of the branched-chain amino acid metabolism, it is speculated that this hyperglycinemia might be due to inhibition of the glycine cleavage system by 2-methyl-butyryl-CoA and isobutyryl-CoA, and that these conditions thus might serve as models for ketotic hyperglycinemia.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Tyrosine peptides, such as L-alanyl-L-tyrosine, have excellent solubility and are potential sources of iv tyrosine. Infusion of L-alanyl-L-U-14C-tyrosine as part of a total parenteral nutrition regimen in the rat at a level of 0.5 mmole/kg/day resulted in rapid labeling of tissue tyrosine pools, production of14CO2, incorporation of14C-labeled tyrosine into protein, and minimal urinary losses (7.7%). Plasma tyrosine levels, however, remained at fasting. Infusion of L-alanyl-L-tyrosine at 2 mmole/kg/day increased plasma tyrosine above fasting levels and maintained tissue tyrosine at levels seen in orally fed control animals without increasing the percent lost in urine (5.5%). Rapid utilization of L-alanyl-L-tyrosine was noted at both infusion levels with no accumulation of peptide noted in plasma. Plasma and tissue free tyrosine pools were rapidly labeled, as was tissue protein. Radioactivity incorporated in tissue protein was shown to be tyrosine after acid hyrolysis.Speculation Tyrosine content of parenteral solutions is limited by poor tyrosine solubility. Tyrosine peptides are soluble and are well utilized during iv feeding of adult rats. This suggests that tyrosine peptides are a reasonable source for supplying the tyrosine requirements of iv fed infants.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

To determine hemodynamic effects of crying, 12 newborn infants recovering from the respiratory distress syndrome (RDS) were studied.When crying, the range of inspiratory esophageal pressure was - 18.8 to −32.5 cm H2O and the range of expiratory pressure was +6.2 to +34.4 cm H2O. The esophageal pressure remained positive for a mean value of 66% of the respiratory cycle. There was a mean significant increase in heart rate of 19 beats/min. The systolic and diastolic blood pressures increased significantly at the beginning of strain to 115 and 135% of the respective control values. There was a progressive decrease in systolic and diastolic pressures during the period of strain and the systolic pressures reached values significantly less than control. With the decrease in systolic and diastolic pressures, there were pronounced reductions in pulse pressures. Three infants reached pulse pressure values less than 1% of control when cries were sustained for nine cardiac cycles.There was a significant mean decrease in arterial oxygen tension (PaO2) of 16.8 mm Hg. There were no changes in arterial carbon dioxide tension (PaCO2), pH, or base excess.Speculation Asphyxiated nconates and infants with RDS often have a compromised circulation with hypoxemia and hypotension. This study suggests that the circulatory status in such infants may be further compromised by extended periods of crying. In three patients who were relatively stable and normovolemic, a profound decrease in pulse pressure was observed when the cry included seven or more cardiac cycles. These transient periods of no aortic flow might be of clinical significance in critically ill infants. The decreased frequency of crying observed in critically ill neonates may be beneficial to both oxygenation and hemodynamic stability.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Chondro-osseous tissue from five patients with diastropic dwarfism was studied by histologie, histochcmical, and electron microscopic methods. The major abnormalities observed were: 1) irregular distribution of chondrocytes undergoing degeneration in the resting cartilage; 2) abnormal distribution of collagen in the resting cartilage; 3) a spectrum of fibrous matrix lesions in the resting cartilage which ranged from focal areas of aggregated collagen fibrils to large cystic lesions in which intracartilagenous ossification occurred; and 4) shortened, irregular cellular columns within the growth plate which were occasionally disrupted by matrix lesions extending from the resting cartilage. These alterations in chondro-osseous morphology have not been observed in any of the other skeletal dysplasias examined to date and appear to be pathognomonic for this disorder.Speculation The basic abnormality in diastropic dwarfism may be a metabolic abnormality in the chondrocyte which predisposes it to cell death or a processing defect in its synthesis of either collagen or proteoglycan. An enzyme deficiency could produce either type of defect and would be consistent with the autosomal recessive inheritance of this disorder.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The unique fragility of the neonatal circulation in response to disease states and various physiologic stimuli is apparent clinically, although underlying mechanisms have not been explored. Accordingly, this report examines and compares the influence on cardiac performance of changes in left ventricular (LV) filling pressure in six conscious, unscdated newborn lambs studied serially at 1 and 3 weeks of age and five adult sheep. All animals were instrumented chronically to assess LV internal dimensions and pressures and cardiac output. At constant heart rate, infusion of saline to comparably high LV end diastolic pressure was associated in the younger newborns with significantly elevated mean arterial pressures (MAP), reduced LV stroke volume, stroke work, and mean fiber shortening when compared to older newborns or adults. A separate analysis of the LV pressure-dimension relationships showed lowest LV compliance in the youngest animals with a progressive increase with age. Thus, these results suggest that the youngest newborns have limited preload reserve related to reduced LV compliance. With volume infusion, sacromeres are stretched fully; the rise in peripheral resistance creates a mismatch between aftcrload and the level of inotropic state. These findings provide a framework for viewing cardiocirculatory adaptation to left-to-right shunt lesions in the human newborn and support the contention that age-dependent, disadvantageous myocardial mechanical factors play a critical role in their clinical course.Speculation The determinants of LV performance can best be described in terms of preload, afterload, and contractile state. The dynamic transition after birth from a single, parallel fetal circulation into separate, independent pulmonary and systemic circuits imposes marked loading alterations on the left ventricle of the newborn. Thus, preload increases dramatically in parallel with a 3-to 4-fold augmentation in pulmonary blood flow; systemic vascular resistance rises when clamping the umbilical cord removes the low resistance placental circulation, and when constriction of the ductus arteriosus occurs. Of course, the presence of a cardiac malformation may further accentuate either preload or aftcrload.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

As a first step toward the use of cats with Gm2gangliosidosis as models for enzyme replacement therapy, we studied plasma clearance, organ disposition, and subcellular localization of human ß-hexosaminidase in normal cats. Plasma half-life of placental ß-hexosaminidase at low doses was 3–4 min; both Hex A and Hex B were cleared at approximately the same rate. The half-life of human plasma ß-Miexosaminidase in contrast, was >60 min. Clearance curves at higher doses approached zero order kinetics, suggesting the existence of a saturable clearance mechanism. Injection of periodate-treated placental ß-Miexosaminidase resulted in a plasma half-life of ∼50 min, strongly suggesting that rapid clearance of both Hex A and Hex B was mediated by carbohydrate-specific mechanisms. Circulatory bypass of liver resulted in plasma half-life of the enzyme of ∼60 min, indicating that the liver was the main clearing organ. As both main feline ß-Miexosaminidase isozymes did not crossreact with antihuman ß-Miexosaminidase immune sera, independent evidence of preferential hepatic uptake was obtained by immunofixation clectrophoresis; immunoelectrophoresis, and immunotitration. The human enzyme detected in liver accounted for ∼80% of the injected dose; small amounts of exogenous enzyme were detected in spleen and kidney. Subcellular fractionation of liver showed that human Hex A and Hex B had entered the lysosomal-vacuolar apparatus of hepatic cells.Speculation Therapeutic applications of lysosomal enzyme replacement in patients with storage diseases are fraught with difficulties. Normal cats infused with human ß-Miexosaminidase can be used to develop enzyme replacement methodologies to be tested in cats with genetic Gm2gangliosidosis. This unique animal model makes it possible to explorein vivorational approaches to therapeutic intervention in human patients.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Lung functions were measured on 13-day-old conjoined thora-copagus twins. Mean values for tidal volume and minute ventilation were 14.8 ml and 1102 ml/min for twin A and 12.8 ml and 963 ml/ min for twin B. Functional residual capacities (FRC) were 35 ml/ kg and 39 ml/kg for twins A and B, respectively. Pulmonary compliance and flow resistance for twin A were 2.8 ml/cm H2O and 75 cm H2O/liter sec−1with 45% of the total work used to overcome elastic resistance. Although values for resistance and work of breathing are within the normal range for studies reported elsewhere, these results tend to be elevated and probably reflect an abnormal state.Speculation With decreasing reluctance by surgeons to separate conjoined thoracopagus twins, data concerning their preoperative respiratory pathophysiology assumes greater importance. Pulmonary function tests on conjoined twins may provide valuable information concerning the feasibility and prognosis for successful separation.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID