摘要:

ExtractPropionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not by acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA.From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.SpeculationThe metabolism of propionate, methylmalonate, and branched chain amino acids is normal in true nonketotic hyperglycinemia. Further investigations will have to show whether the observed block in the glycine cleavage reaction to CO2, NH3, and a single-carbon tetrahydrofolate derivative represents the primary enzymatic defect. In view of the four enzymatic steps involved in this complex reaction, it may well be that true nonketotic hyperglycinemia also represents a heterogeneous syndrome. The elevated glycine concentrations in the central nervous system (CNS) may play a significant role in the development of the neurologic symptoms.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractTwenty-six infants weighing less than 1,300 g at birth were divided into pairs according to birth weight (900–1,100 and 1,101–1,300 g) and gestational age (“appropriate” (AGA) = mean 31 weeks; and “small” (SGA) = mean 34 weeks). One member of the pairs was then allocated randomly to one of two treatment regimens with oral sodium bicarbonate.Group Awas treated whenever base excess was greater than −8 mEq/liter as detected on twice weekly testing and/or when suspected to be acidotic from failure to gain weight. Ingroup B, base excess was maintained within 1 SD of normal (-3.2 ± 1.7 mEq/liter). The infants received Enfalac 200 ml/kg/24 hr, at 67 cal/100 ml, with vitamin D 400 IU/24 hr added from age 2 weeks.The following measurements were made: daily weight, weekly length, skinfold thickness, head circumference, twice weekly blood pH, PaCO2, base excess, and weekly plasma total calcium, ionic calcium, total magnesium, inorganic phosphorus, and total protein.There were six pairs each of AGA and SGA infants and two unpairedgroup Ainfants. Weekly weight gains did not differ betweengroup Aandgroup Bor between AGA and SGA. Length increment was greater in AGA than in SGA babies (0.94 ± 0.02 us 0.85 ± 0.04 cm/week) but not significantly so (P< 0.1), and ingroup Bbabies compared togroup Ababies (0.973 ± 0.029 vs 0.83 ± 0.037 cm/week) (P< 0.01).Plasma pH was lower ingroup A(7.23 ± 0.02) than ingroup B(7.30 ± 0.02) and calcium ion activity higher (group A2.72 ± 0.04;group B2.51 ±0.06 mEq/liter) between ages 20 and 29 days. Plasma magnesium was higher ingroup A(1.77 ± 0.04 mEq/liter) than ingroup B(1.56 ± 0.06 mEq/liter) from age 20 to 39 days. Inorganic phosphorus concentrations were consistently higher ingroup Athan ingroup B, but the differences did not reach significance. Mean total protein concentrations did not rise above 4.5 g/100 ml and tended to be higher in babies ofgroup Athan ofgroup B.Bone age was retarded in all babies. Radiographs available for 7 of 13 SGA infants were normal, whereas 6 of 11 radiographs of AGA babies showed some osteoporotic changes.SpeculationCareful control of late metabolic acidosis in infants < 1.3 kg birth weight results in less ionic hypercalcemia and improved growth in length. In the more immature AGA infants, radiologic osteoporosis was seen. Mineral and protein content of formula currently used for feeding infants of less than 1,300 g birth weight is inappropriate to their requirements for growth.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractInfants of two groups, one of 16, one of 14 infants, who weighed < 1.3 kg at birth (mean 1.01 ± 0.05 kg), were studied from age 14 days until they reached 1.8 kg body weight. Infants were pair-matched for gestational age and birth weight and one member was randomly allocated to two treatment groups. Infants ingroup Areceived no calcium supplement and those ingroup Breceived calcium lactate, 800 mg/kg/24 hr, in divided doses with each feed. All were fed “Improved” SMA, 200 ml/kg/24 hr, 160 cal/kg/24 hr, and were given a multivitamin preparation containing 500 IU vitamin D2/dose.The infants' weekly length gain did not differ between groups (1.08 ± 0.04 cm/week vs 1.11 ± 0.04 cm/week; mean ± SEM). Mean weight and head cercumference increments also were similar (group A, 163 ± 6 g/week; 1.12 ±0.03 cm/week;group B, 170 ± 6 g/week and 1.18 ± 0.03 cm/week).An increase in blood pH from 7.33 ± 0.01 to 7.41 ± 0.01 (P< 0.01) ingroup Ababies was associated with a decrease in PCO2from 44.2 ± 1.0 to 38.9 ± 1.4 mm Hg. Values remained unchanged with age ingroup Bbabies. After institution of calcium supplementation, base excess values differed transiently between groups (at age 5 weeks,group A−0.16 ± 0.56 mEq/liter,group B−1.17, ± 0.76 mEq/liter;P< 0.05).Mean ionic calcium values remained unchanged ingroup A(2.37 ± 0.06 mEq/liter), but increased slightly from 2.42 ± 0.06 to 2.57 ±0.04 mEq/liter ingroup B(P< 0.05).Total plasma calcium differed transiently between groups after calcium supplementation had started ingroup B(Group A, 4.53 ± 0.08 mEq/liter;group B, 4.82 ± 0.12 mEq/liter;P< 0.05), and plasma Mg and P levels were lower ingroup Bbabies than ingroup Ababies (P< 0.01). All infants remained somewhat hypoproteinemic throughout the study; mean values of plasma total protein averaged 4.5 g/100 ml.Mean urinary excretion rates of calcium initially were 0.17 mEq/kg/24 hr ingroup Ababies and 0.18 mEq/kg/24 hr ingroup Binfants, and no increase was seen with calcium supplementation.Fecal excretion of calcium (percentage of intake) decreased from 70% to 33% ingroup Bbabies after calcium supplementation. Calcium retention rates (mEq/kg/24 hr) were similar in both groups initially but increased subsequently ingroup Bfrom 1.20 to 7.33 mEq/kg/24 hr and were 3 times as high ingroup Bthan ingroup Aduring the second and third balances.Urinary phosphorus excretion was initially similar in both groups (group A, ISA ± 2.2 mg/kg/24 hr;group B, 32.4 ± 5.5 mg/kg/24 hr), but decreased to half this value in infants ofgroup Bafter calcium supplementation had started (P< 0.02).Group Binfants showed a higher percentage fecal fat excretion thangroup Ainfants during the second and third balance.In 9 of 10 paired radiographs of the knee and tibiagroup Binfants showed better defined bone texture and/or wider cortices than didgroup Ainfants.We suggest that prevention of the “bone disease of very low birth weight (VLBW) infants” may be accomplished by suitable calcium supplements.SpeculationAs a consequence of their special requirements and the unavailability of appropriately constituted infant formulas, infants born very prematurely fail to achieve intrauterine accretion rates for many minerals. Postnatal growth may also be jeopardized. We believe that for optimal postnatal growth infants born very prematurely require sufficient nutrients to parallel intrauterine accretion rates.SpeculationAs a consequence of their special requirements and the unavailability of appropriately constituted infant formulas, infants born very prematurely fail to achieve intrauterine accretion rates for many minerals. Postnatal growth may also be jeopardized. We believe that for optimal postnatal growth infants born very prematurely require sufficient nutrients to parallel intrauterine accretion rates.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractA simple and rapid method for determination of the hypoxanthine and xanthine concentration in plasma and urine is described. The method is based on the principle that oxygen is consumed quantitatively when hypoxanthine and xanthine are oxidized to urate by xanthine oxidase. By using Henry's law a direct measure of the hypoxanthine and xanthine concentration is obtained.The method determines these oxypurines in volumes of 200 μl in concentrations less than 5 μmol/liter in about 5 min. The average precision in the range of 0–50 μmol/liter is 2.6 μmol/liter. Of the added hypoxanthine, 99 102% is recovered in plasma. Even though xanthine oxidase is a rather nonspecific enzyme, experiments show that this method is highly specific during physiologic conditions.SpeculationOther purines which can be metabolized to hypoxanthine can be determined by this method. For instance, inosine, which is metabolized to hypoxanthine by nucleoside phosphorylase in the presence of phosphate, might also be determined according to this method.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe effects of corticosteroid treatment on growth and skeletal maturation were evaluated in 189 children with severe asthma who were referred for care at a residential treatment center. Height age on admission was significantly retarded in 8–10% of patients who had received little corticosteroid treatment previously and in 35% of patients who had taken steroids daily for more than 2 years. Children who had been treated with steroids intermittently or on alternate days were comparable to those who had taken steroids rarely. During an average residential period of 17 months, patients whose daily steroid treatment was discontinued had a relative gain in height age of 5 months; children who were started on daily steroids had a 5-month delay in growth. Evaluation of skeletal maturation at the time of admission revealed that skeletal age was more retarded than height age in the boys and less retarded than height age in the girls. During the period of residence, the changes in bone age paralleled the changes in height age.SpeculationSuppression of growth is a frequent complication in asthmatic children who receive prolonged treatment with corticosteroids. In some patients the suppression of growth may result in permanent dwarfism. However, no information is currently available on the adult heights of patients who have received prolonged corticosteroid therapy during childhood.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractDeterminations of cell electrophoretic mobility at low ionic strength and of ghost sialic acid content show that erythrocytes from umbilical cord blood and from adult donors are identical in these two glycoprotein-related properties. Using streak deflection electro-phoresis in 16.5 mM Tris-acetic acid buffer, pH 7.4, no increased streak width indicating electrophoretic heterogeneity could be detected when mixed suspensions of adult and umbilical cord blood erythrocytes were compared with suspensions of adult cells alone. Sialic acid content of 100 nmol/mg protein were obtained for both populations of cells.SpeculationUnlike cells involved in rapid proliferation, which carry higher negative surface charge densities than those which are non-proliferating, the umbilical cord erythrocyte exhibits the surface charge characteristics of a fully mature cell.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThis investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1α-hydroxyvitamin D3(1α-OH-D3) on children with nutritional rickets, “pseudodeficiency” rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3or 1α-OH-D3to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 /μg/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1α-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.SpeculationThe similarity of action of 1,25-(OH)2-D3and 1α-OH-D3observed in the present study presents additional evidence that 1α-OH-D3can be considered a valuable substitute for the hormonal form of cholecalciferol, especially for the management of children with chronic renal failure, hypoparathyroidism, or pseudo-deficiency rickets. In this latter disease, the active therapeutic doses of either drug appear to be greater than the amount required for the treatment of simple nutritional rickets. This observation indicates that investigations on the pathogenesis of pseudodeficiency rickets must be continued in order to confirm or invalidate the hypothesis suggested by us and others that this inherited disorder might be related to a deficit in 25-hydroxycholecalciferol 1α-hy-droxylase.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe therapeutic response to chemically synthesized 1α-hydroxy-cholecalciferol (1α-OH-D3) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD). The daily maintenance dose for vitamin D2, to prevent signs of vitamin D deficiency in these patients, was 40–54.5 μ/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2resulted in the ultimate reappearance of the vitamin D depletion syndrome inpatients 1and2(Figs. 1 and 2). The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD.Treatment with 1α-OH-D3by mouth in all three patients at dose levels of 1–3 μg/24 hr (80–100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1, 2, and 4). Rickets healed in 7–9 weeks on 1α-OH-D3alone (Fig. 3) The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of 1α-OH-D3was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal.Because the synthesis of 1α-OH-D3is simpler than for 1α,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1α-OH-D3to be the agent of choice for treatment of this and analogous diseases.SpeculationVitamin D dependency or pseudodeficiency rickets is believed to be an inborn error of vitamin D hormone biosynthesis. The putative abnormal enzyme is 25-hydroxycholecalciferol 1-hydroxylase in the recessively inherited trait. Consequently, this experiment of nature offers a special opportunity to examine the requirement in human subjects, for 1α -hydroxyvitamin D3, metabolites.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractNear term fetal monkey livers were perfused with a closed recirculating system and a defined perfusion medium. Livers from normal fetal animals were able to release glucose rapidly into the perfusate when they were exposed to glucagon, cyclic AMP, or an aglycemic perfusate, but they did not remove glucose rapidly from the perfusate, synthesize glycogen, or activate liver glycogen synthetase in response to hyperglycemia (Figs. 1, 2, and 3; Table 1). Insulin decreased glucose mobilization in response to aglycemia, but did not stimulate glucose uptake during hyperglycemia; insulin activated glycogen synthetase (Table 1; Figs. 1 and 3). Livers from fetuses of streptozotocin-treated mothers and livers from 2-week-old neonates released more glucose into the perfusate in response to aglycemia then did livers from normal fetal monkeys (Fig. 4). These observations support the possibility that neonatal monkey liver is capable of rapidly mobilizing glucose during periods of hypo-glycemia but is unable to take up glucose and store glycogen rapidly during periods of hyperglycemia.SpeculationIncomplete development of glycogen synthetic mechanisms in early postnatal life may contribute to decreased liver glycogen reserves. These decreased reserves may then be inadequate for maintaining normoglycemia during periods of increased glucose uptake or utilization by peripheral tissue.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractA rapid, sensititive radioimmunoassay for thyroxine (T4) is described which requires a specimen of dried blood on filter paper. One milliliter of glycine-acetate buffer containing anti-T4antibody, tracer T4, and sodium salicylate is added to a tube containing a 1/8-inch dot of the filter paper specimen. After, incubation overnight, bound and free hormone are separated by addition of dextran-coated charcoal. Quantitation is obtained using a standard curve prepared from dots of dried blood samples with known T4content. The dot remains in the solution throughout the procedure. Recovery of T4is 95% and intra- and interassay coefficients of variation are both less than 10%. The mean T4content of 983 samples from 3-day-old infants was 189 ± 48 pg T4/dot (mean SD). This corresponds to the T4 in 1.5 μl plasma, and thus the estimated plasma T4in these infants is 12.6 ± 3.2 μg T4/100 ml. Nine neonates had repeated samples in which the T4content was lower than 2 SD below the mean. All of these infants had normal cord thyroid-stimulating hormone (TSH) concentrations and thus presumably do not have primary hypothyroidism. The method …

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID